naloxone and Fever

Substance abuse is a significant health problem in the adolescent population. Prevention is a formidable challenge, but attempts at discouraging experimentation in early adolescence and the promotion of healthy adult role models may be effective strategies. Questions that may elicit a history suggestive of abuse should be a routine part of the adolescent medical history. Pediatricians should be familiar with the important clinical findings resulting from intoxication with the various substances of abuse and should be able to recognize the "telltale" signs of abuse. Effective management is based on attention to the basics of life support, careful attention to the physical findings, and judicious use of specific therapeutic agents. Above all, a compassionate attitude should prevail if acute-phase recovery and long-term rehabilitation are to be successful.

Topics: Absorption; Adolescent; Adult; Alcoholic Intoxication; Amphetamines; Anti-Anxiety Agents; Benzodiazepines; Cocaine; Diagnosis, Differential; Female; Fever; Glucose; Hallucinogens; Humans; Hypotension; Illicit Drugs; Lysergic Acid Diethylamide; Marijuana Abuse; Mescaline; Methaqualone; Mushroom Poisoning; Naloxone; Narcotics; Nitrites; Poisoning; Solvents; Substance-Related Disorders

Of the effects of morphine and endogenous opioid peptides on thermoregulation, the one which is most likely to be of physiologic significance is hyperthermia. This increase in body temperature is the result of coordinated changes in both physiological and behavioral thermoregulatory activities and, like fever, reflects an increase in the level about which body temperature is regulated. Morphine, endogenous opioid peptides and other opioids such as pentazocine all cause hyperthermia, but the considerable variation in the dose of naloxone required to antagonize the different agonists indicates that more than one type of opiate receptor is involved in these pharmacologic responses. The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine. However, methionine-enkephalin is less readily antagonized by naloxone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor.

Topics: Animals; Body Temperature; Body Temperature Regulation; Fever; Morphine; Naloxone; Narcotics; Rats; Receptors, Opioid; Restraint, Physical

This study was designed to test the hypothesis that the immune changes seen during in vivo whole body hyperthermia are mediated by elevations in the plasma concentrations of either catecholamines, growth hormone or beta-endorphins. Eight healthy volunteers were immersed in a hot water bath (WI; water temperature 39.5 degrees C) for 2 h during which their rectal temperature rose to 39.5 degrees C. In a single blind, randomized, cross-over study the stress hormone effects were blocked one at a time by administration of propranolol, somatostatin or naloxone; the results were compared to those obtained during saline infusion (control). Blood samples were collected before, at the end of 2 h of WI (body temperature 39.5 degrees C), and 2 h later. Hormone blockade did not abolish the hyperthermia-induced recruitment of natural killer (NK) cells to the blood, and no influence was observed on the percentages or concentrations of any other subpopulations of blood mononuclear cells, except that the number of cluster designation (CD)3+ cells slightly increased after hyperthermia only in the propranolol experiment. Furthermore, the NK cell activity, both unstimulated and interferon-alpha or interleukin-2 stimulated, did not differ from the control situation. It is of interest, however, that somatostatin partly abolished the hyperthermia induced increase in the neutrophil number. Based on these data and previous results showing that growth hormone infusion increases the concentration of neutrophils in the blood, it is suggested that growth hormone is at least partly responsible for hyperthermia induced neutrocytosis.

Topics: Adult; Cross-Over Studies; Fever; Hot Temperature; Humans; Immersion; Killer Cells, Natural; Kinetics; Leukocyte Count; Lymphocyte Count; Male; Naloxone; Neutrophils; Propranolol; Somatostatin

Studies examined the role of growth hormone, catecholamines, and beta-endorphins in changes in natural killer cell activity, subtypes of blood mononuclear cells, and leukocyte concentration in response to hot water immersion in humans. The response of leukocytes and neutrophils to 2 hours of hot water immersion and simultaneous administration of propranolol, somatostatin, naloxone, or isotonic saline are reported.

Topics: Adrenergic beta-Antagonists; Adult; Body Temperature; Endorphins; Fever; Growth Hormone; Hormone Antagonists; Hot Temperature; Humans; Immersion; Killer Cells, Natural; Leukocytes; Leukocytes, Mononuclear; Leukocytosis; Male; Naloxone; Narcotic Antagonists; Neutrophils; Propranolol; Sodium Chloride; Somatostatin; Water

Naloxone, an opioid antagonist, and meptazinol, an opioid antagonist with agonist properties, were tested in a double-blind placebo-controlled trial in 24 Ethiopian patients with louse-borne relapsing fever. The potentially fatal Jarisch-Herxheimer reaction (J-HR), which invariably follows tetracycline treatment of the disease, was unaffected by naloxone, 30-40 mg intravenously, but was diminished by meptazinol, 300-500 mg intravenously. Compared with naloxone and placebo, meptazinol reduced the clinical severity of the reaction, significantly delayed and shortened its chill phase, delayed the rise in temperature, and reduced peak temperature and changes in pulse and respiratory rates and leucocyte count. High-dose corticosteroids given before or at the time of tetracycline treatment failed to alter the reaction, which is thought to result from release of endotoxin-like substances. Meptazinol is the first effective treatment for the J-HR of louse-borne relapsing fever. This finding suggests a role for endogenous opioids in the pathogenesis of the J-HR.

Topics: Adolescent; Adult; Azepines; Clinical Trials as Topic; Double-Blind Method; Endotoxins; Fever; Humans; Infusions, Parenteral; Meptazinol; Naloxone; Prednisolone; Relapsing Fever; Spirochaeta; Tetracycline

This study aims to explore the contribution of endocannabinoids on the cascade of mediators involved in LPS-induced fever and to verify the participation of prostaglandins and endogenous opioids in fever induced by anandamide (AEA). Body temperature (Tc) of male Wistar rats was recorded over 6h, using a thermistor probe. Cerebrospinal fluid concentration of PGE2 and β-endorphin were measured by ELISA after the administration of AEA. Intracerebroventricular administration of the CB1 receptor antagonist AM251 (5μg, i.c.v.), reduced the fever induced by IL-1β (3ng, i.c.v.), TNF-α (250ng, i.c.v.), IL-6 (300ng, i.c.v.), corticotrophin release factor (CRH; 2.5μg, i.c.v.) and endothelin (ET)-1 (1pmol, i.c.v.), but not the fever induced by PGE2 (250ng, i.c.v.) or PGF2α (250ng, i.c.v.). Systemic administration of indomethacin (2mgkg(-1), i.p.) or celecoxib (5mgkg(-1), p.o.) reduced the fever induced by AEA (1μg, i.c.v.), while naloxone (1mgkg(-1), s.c.) abolished it. The increases of PGE2 and β-endorphin concentration in the CSF induced by AEA were abolished by the pretreatment of rats with AM251. These results suggest that endocannabinoids are intrinsically involved in the pyretic activity of cytokines (IL-1β, TNF-α, IL-6), CRH and ET-1 but not the PGE2 or PGF2α induced fevers. However, anandamide via CB1 receptor activation induces fever that is dependent on the synthesis of prostaglandin and opioids.

Topics: Animals; Arachidonic Acids; beta-Endorphin; Body Temperature; Corticotropin-Releasing Hormone; Cytokines; Endocannabinoids; Endothelin-1; Fever; Interleukin-1beta; Interleukin-6; Male; Naloxone; Narcotic Antagonists; Piperidines; Polyunsaturated Alkamides; Prostaglandins; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Tumor Necrosis Factor-alpha

A large body of evidence supports the existence of an endogenous glutamate system that tonically modulates body temperature via N-methyl-d-aspartate (NMDA) receptors. Ketamine and magnesium, both NMDA receptor antagonists, are known for their anesthetic, analgesic and anti-shivering properties. This study is aimed at evaluating the effects of ketamine and magnesium sulfate on body temperature in rats, and to determine the type of interaction between them. The body temperature was measured by insertion of a thermometer probe 5cm into the colon of unrestrained male Wistar rats (200-250g). Magnesium sulfate (5 and 60mg/kg, sc) showed influence neither on baseline, nor on morphine-evoked hyperthermic response. Subanesthetic doses of ketamine (5-30mg/kg, ip) given alone, produced significant dose-dependent reduction in both baseline colonic temperature and morphine-induced hyperthermia. Analysis of the log dose-response curves for the effects of ketamine and ketamine-magnesium sulfate combination on the baseline body temperature revealed synergistic interaction, and about 5.3 fold reduction in dosage of ketamine when the drugs were applied in fixed ratio (1:1) combinations. In addition, fixed low dose of magnesium sulfate (5mg/kg, sc) enhanced the temperature lowering effect of ketamine (1.25-10mg/kg, ip) on baseline body temperature and morphine-induced hyperthermia by factors of about 2.5 and 5.3, respectively. This study is the first to demonstrate the synergistic interaction between magnesium sulfate and ketamine in a whole animal study and its statistical confirmation. It is possible that the synergy between ketamine and magnesium may have clinical relevance.

Topics: Animals; Body Temperature; Dose-Response Relationship, Drug; Drug Interactions; Excitatory Amino Acid Antagonists; Fever; Hypothermia, Induced; Ketamine; Magnesium Sulfate; Male; Morphine; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Thermometers; Time Factors

The current study was designed to explore the antinociceptive, antiinflammatory and antipyretic activity of pistagremic acid (PA), isolated from Pistacia integerima bark in various animal paradigms. The results illustrated significant inhibition of noxious stimulation in acetic acid induced writhing test with maximum effect of 68% at 10mg/kg i.p. In tail immersion test, pretreatment with PA demonstrated marked activity during various assessment times in a dose dependent manner. The maximum pain inhibition was 59.46% at 10mg/kg i.p. after 90 min of PA treatment. However, the injection of naloxone did not antagonize this induced effect. PA significantly ameliorated post carrageenan induced edema dose dependently during various stages of inflammation. The effect was most dominant (60.02%) after 3(rd) h of drug administration when examined for 5h. Similarly, it provoked dose dependent antipyretic effect in febrile mice with maximum of 60.04% activity at 10mg/kg i.p. after 3rd hour of PA post treatment. Furthermore, molecular docking was carried out to understand the binding mode of PA. From the docking study it was observed that PA fits well in the active site of COX-2 enzyme due to hydrogen and hydrophobic moiety interactions to the important active site of molecule. In conclusion, PA possesses strong peripheral and central antinociceptive activity independent of opioidergic effect which was augmented by its anti-inflammatory and antipyretic activities.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Female; Fever; Inflammation; Male; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Molecular Structure; Naloxone; Pain; Pistacia; Triterpenes

Topics: Aged; Analgesics; Brain; Drug Interactions; Duloxetine Hydrochloride; Female; Fever; Humans; Magnetic Resonance Imaging; Naloxone; Narcotic Antagonists; Narcotics; Neuroimaging; Postoperative Complications; Thiophenes; Tilidine

Artemisia scoparia (redstem wormwood) locally known as jhahoo or jaukay, is traditionally used in pain, inflammation and febrile conditions. So far, little or no scientific work has been reported to validate its folk uses in the alleviation of pain, fever and inflammation. The present study was designed to explore the analgesic, anti-inflammatory and antipyretic effects of the Artemisia scoparia hydromethanolic extract (ASHME), and to validate its traditional use in Asia.. This study made use of thermal (hot plate induced) and chemical (acetic acid induced) nociception models in mice. In addition, the mechanism of antinociception in hot plate test was further evaluated in the presence of caffeine (10mg/kg), naloxone (2mg/kg) and monosodium glutamate (1g/kg). While carrageenan induced rat paw edema and yeast induced mouse pyrexia models were used to test the anti-inflammatory and antipyretic activities.. Administration of single intraperitoneal doses (400mg/kg and 800 mg/kg) of ASHME significantly reduced the carrageenan induced paw edema in rats (P<0.05, P<0.001) by 54% and 74%, increased the thermal nociception time in the hot plate test up to 2- and 2.5-fold (P<0.01, P<0.001), inhibited the acetic acid induced writhings in mice by 41.12% and 61.53% (P<0.001), and attenuated the yeast induced pyrexia in mice by nearly 74% and 90% respectively (P<0.01, P<0.001). Caffeine (10mg/kg), naloxone (2mg/kg) and monosodium glutamate (1g/kg) significantly (P<0.001) abolished the anti-nociceptive response of ASHME (400mg/kg).. These findings suggest that the Artemisia scoparia hydromethanolic extract of ASHME possesses anti-nociceptive, anti-inflammatory and antipyretic potentials, which support its use, for the said conditions, in traditional medicine and should be further exploited for its use in clinical medicine.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Artemisia; Caffeine; Carrageenan; Edema; Female; Fever; Herb-Drug Interactions; Male; Methanol; Mice; Mice, Inbred BALB C; Naloxone; Pain; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Sodium Glutamate

Pyrexia, algesia and inflammation are associated with several pathological conditions. Synthetic drugs available for the treatment of these conditions cause multiple unwanted effects. Several studies are ongoing worldwide to find natural healing agents with better safety profile. The current study was thus aimed at evaluating antipyretic, analgesic and anti-inflammatory activities of the methanolic extract of whole plant of V. betonicifolia (VBME).. VBME was employed to assess antipyretic activity in yeast induced hyperthermia. Analgesic profile was ascertained in acetic acid induced writhing, hot plat and tail immersion test. Nevertheless, the anti-inflammatory activity was tested in carrageenan induced paw edema and histamine induced inflammatory tests. BALB/c mice were used at test doses of 100, 200 and 300 mg/kg body weight intra peritoneally (i.p).. In yeast induced pyrexia, VBME demonstrated dose dependently (78.23%) protection at 300 mg/kg, similar to standard drug, paracetamol (90%) at 150 mg/kg i.p. VBME showed a dose dependent analgesia in various pain models i.e. acetic acid, hot plat and tail immersion having 78.90%, 69.96% and 68.58% protection respectively at 300 mg/kg. However, the analgesic action of VBME was completely antagonized by the injection of naloxone like opiate antagonists. Similarly carrageenan and histamine induces inflammation was significantly antagonized by VBME, 66.30% and 60.80% respectively at 300 mg/kg.. It is concluded that VBME has marked antipyretic, analgesic and anti-inflammatory activities in various animal models and this strongly supports the ethnopharmacological uses of Viola betonicifolia as antipyretic, analgesic and anti-inflammatory plant.

Topics: Acetaminophen; Acetic Acid; Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Behavior, Animal; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Female; Fever; Histamine; Hot Temperature; Inflammation; Male; Mice; Mice, Inbred BALB C; Naloxone; Narcotic Antagonists; Pain; Phytotherapy; Plant Extracts; Tail; Viola; Yeasts

To study the effects and mechanism of naloxone on the febrile response in IL-1beta-induced fever rats.. The fever model was established by intracerebroventricular injection of IL-1beta in rats. The effect of naloxone on the body temperature of feverrats was observed. The contents of cAMP in hypothalamus and AVP in VSA were detected.. Naloxone alleviated IL-1beta-induced fever and the contents of cAMP in hypothalamus and AVP in VSA were correspondingly decreased (P < 0.01).. Naloxone could inhibit IL-1beta-induced fever in rats, and the mechanism might be due to inhibiting synthesis of cAMP in hypothalamus and promoting release of AVP in VSA.

Topics: Animals; Arginine Vasopressin; Cyclic AMP; Fever; Hypothalamus; Male; Naloxone; Rats; Rats, Sprague-Dawley; Septum of Brain

We evaluated the interaction between electroacupuncture (EA)-induced antinociception and an endogenous anti-analgesic system. EA was applied to the ST-36 acupoint for 45 min in male Sprague-Dawley rats, and pain thresholds were assessed by the hind-paw pressure test. EA produced a marked increase in pain thresholds and its antinociceptive action was completely reversed by naloxone (5 mg/kg). The analgesic effects of subcutaneous morphine (7 mg/kg) following EA stimulation were significantly attenuated. The attenuation of morphine analgesia was inversely proportional to the time intervals between EA termination and morphine injection, and the effect was not observed 120 min after EA stimulation. The analgesic effects of i.t. morphine (10 microg), but not i.c.v. morphine (25 microg), following EA were also attenuated. On the other hand, systemic morphine (7 mg/kg)-induced hyperthermia was not affected by EA. Moreover, i.c.v. morphine, but not i.t. morphine, produced hyperthermia. The i.c.v. morphine-induced hyperthermia was not affected by EA, similar to i.c.v. morphine analgesia. These results suggest that the attenuation of morphine analgesia following EA, that is, the activation of an endogenous anti-analgesic system, is closely related to the activation of an analgesic system by EA and that the spinal cord plays a critical role in the activation of the endogenous anti-analgesic systems.

Topics: Analgesia; Analgesics, Opioid; Animals; Body Temperature; Constipation; Electroacupuncture; Endocrine System; Endorphins; Fever; Injections, Intraventricular; Injections, Spinal; Male; Microinjections; Morphine; Naloxone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Respiratory Insufficiency; Spinal Cord

Effect of moclobemide, a selective monoamine oxidase-type A enzyme inhibitor, was investigated on the body temperature of male mice. Moclobemide (15-30 mg kg(-1), i.p.) produced significant reductions of body temperature in both normal and yeast-induced hyperthermic male mice. The hypothermic effect of moclobemide was moderate and short-lasting. Moclobemide-induced hypothermia was not antagonized by previous administration of prazosin (10 and 20 mg kg(-1), s.c.), propranolol (5, 10, and 20 mg kg(-1), s.c.), haloperidol (2 and 10 mg kg(-1), s.c.), atropine (10 and 20 mg kg(-1), s.c.), mepyramine (25 and 50 mg kg(-1), s.c.), or methysergide (0.5, 1, and 2 mg kg(-1), s.c.). Pretreatment with the opioid antagonist naloxone (10 mg kg(-1), s.c.), however, was able to reverse the hypothermic effect of moclobemide (30 mg kg(-1), i.p.) in both normal and yeast-induced hyperthermic mice. The present results indicate a possible role for central opioid receptors in the hypothermic effect of moclobemide. Also, a peripheral component for this effect of moclobemide at the mitochondria of peripheral tissues is suspected. The peripheral tissue mitochondria could be considered a common target for moclobemide and opioids actions on body temperature.

Topics: Animals; Body Temperature; Body Temperature Regulation; Dose-Response Relationship, Drug; Fever; Hypothermia; Male; Methysergide; Mice; Moclobemide; Monoamine Oxidase Inhibitors; Naloxone; Narcotic Antagonists; Receptors, Opioid; Saccharomyces cerevisiae; Sex Factors

Morphine (MOR) is known to inhibit maternal behavior and induce hyperthermia; at appropriate doses, concurrent administration of naloxone (NAL) counteracts its disruption of maternal behavior but not the hyperthermia. We used these findings to evaluate the view that lactating rats terminate nursing due to intolerable hyperthermia. After a dam-litter separation of 4 h on Day 7 postpartum (PP), mother-litter interactions were observed continuously for 1 h. One hour before reunion, the dams received two injections (1 ml/kg ip each) of saline (SAL), MOR (20 mg/kg) and/or NAL (1 mg/kg) in the following combinations (n = 7 each): SAL + SAL, SAL + NAL, MOR + SAL or MOR + NAL. MOR profoundly disrupted maternal behavior, thereby preventing litter weight gains; these effects were completely counteracted by NAL, which alone had no discernible effects. In contrast, MOR-induced hyperthermia (approximately 0.7 degrees C increase in each hour, before and after reunion with pups) was not antagonized by NAL at the doses used. Thus, an additional 0.7-1.4 degrees C of body temperature (T) did not delay the onset or reduce the duration of nursing compared with SAL-treated controls. Further, there were no group differences in behaviors displayed both shortly before and after a nursing bout that included milk ejections or in the resumption of nursing. Together with earlier methodological and empirical criticisms of the thermal control theory, as well as knowledge about the somatosensory determinants of nursing, the present results suggest that nursing bouts in lactating rats are not limited by the mother's T.

Topics: Animals; Body Temperature; Drug Combinations; Female; Fever; Injections, Intraperitoneal; Lactation; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Rats; Rats, Long-Evans; Reference Values; Sodium Chloride

Intravenous heroin self-administration in trained rats was accompanied by robust brain hyperthermia (+2.0-2.5 degrees C); parallel changes were found in the dorsal and ventral striatum, mediodorsal thalamus, and deep temporal muscle. Temperature began to increase at variable latency after a signal of drug availability, increased reliably (approximately 0.4 degrees C) before the first lever press for heroin, increased further (approximately 1.2 degrees C) after the first heroin injection, and rose more slowly after the second and third injections to stabilize at an elevated plateau (39-40 degrees C) for the remainder of the session. Brain and body temperature declined slowly when drug self-administration was terminated; naloxone precipitated a much more rapid decrease to baseline levels. Changes in temperature were similar across repeated daily sessions, except for the increase associated with the first self-administration of each session, which had progressively shorter latency and greater acceleration. Despite consistent biphasic fluctuations in movement activity associated with heroin self-administrations (gradual increase preceding the lever press, followed by an abrupt hypodynamia after drug infusion), mean brain temperature was very stable at an elevated plateau. Only mean muscle temperature showed evidence of biphasic fluctuations (+/-0.2 degrees C) that were time locked to and correlated with lever pressing and associated movements. Drug- and behavior-related changes in brain temperature thus appear to reflect some form of neuronal activation, and, because temperature is a factor capable of affecting numerous neural functions, it may be an important variable in the control of behavior by drugs of abuse.

Topics: Animals; Behavior, Animal; Brain; Corpus Striatum; Fever; Heroin; Heroin Dependence; Injections, Intravenous; Male; Naloxone; Rats; Rats, Long-Evans; Reaction Time; Self Administration; Temporal Muscle; Thalamus

The possible involvement of nitric oxide (NO) in morphine-induced catalepsy and hyperthermia was studied in morphine-dependent rats. Four days repeated injection regimen was used to induce morphine dependence, which was assessed by naloxone challenge (0.5 mg x kg(-1), s.c.). Pretreatment of rats with the NO synthase inhibitor, N(G)-nitro-L-arginine (L-NA, 8 mg x kg(-1) twice daily, i.p.) potentiated the cataleptic response of morphine as shown by a rightward shift in the morphine-log dose-response curve. Prior treatment of rats with the NO precursor, L-arginine (200 mg x kg(-1), twice daily, i.p.) abolished the potent effect of L-NA and restored the cataleptic scores to levels similar to those of morphine-dependent rats. The same dose of L-NA significantly blocked morphine-induced hyperthermia at the dose levels of morphine (15-105 mg x kg(-1)) and this effect was reversed by L-arginine. These data provide the first experimental evidence that NO is involved in morphine induced catalepsy and hyperthermia and demonstrated that blockade of NO synthesis may suggest a dangerous interaction with opioids in the control of motor function.

Topics: Animals; Arginine; Catalepsy; Enzyme Inhibitors; Fever; Male; Morphine; Morphine Dependence; Naloxone; Narcotic Antagonists; Narcotics; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Rats; Substance Withdrawal Syndrome

Effects of excitatory aminoacids (EAAs) aspartate (ASP) and glutamate (GLU) in a low (50 ng, i.c.) and high dose (20 micrograms, i.c.), were studied on nociception, catalepsy and rectal temperature in albino rats. Both ASP and GLU altered the tail flick reaction time to thermal stimulation in a dose dependent manner, increasing it with low doses and reduced with high doses. Naloxone (10 micrograms, ic) antagonized the anti-nociceptive effect of EAAs while ketamine (10 micrograms, ic)-a NMDA receptor antagonist antagonized the hyperalgesic effect. These EAAs also antagonized catalepsy induced by haloperidol, chlorpromazine, trifluoperazine and morphine. Both ASP and GLU produced a hyperthermic response in all animals, including those in which hypothermia was induced by reserpine. These EAAs produced a comparable central modulatory effects on nociception, catalepsy and core temperature.

Topics: Adrenergic Uptake Inhibitors; Analgesia; Analgesics, Opioid; Animals; Aspartic Acid; Body Temperature; Catalepsy; Chlorpromazine; Dopamine Antagonists; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists; Fever; Glutamic Acid; Haloperidol; Hypothermia; Injections, Subcutaneous; Ketamine; Male; Morphine; Naloxone; Narcotic Antagonists; Nociceptors; Rats; Reserpine; Trifluoperazine

The ability of naloxone to block the effects of the benzodiazepines chlordiazepoxide and diazepam was evaluated in Swiss and Balb/c mice subjected to the light/dark choice test of anxiety or to a choice paradigm for measuring spontaneous exploratory behaviour. In Swiss mice, naloxone (5 or 10 mg/kg) completely or partially suppressed the anxiolytic-like effects of chlordiazepoxide (5 mg/kg) and diazepam (1 mg/kg) in the light/dark test. Naloxone alone was ineffective. None of these compounds affected locomotion in the free exploratory test. In Balb/c mice, naloxone did not reduce the anxiolytic-like action of benzodiazepines in the light/dark test. Moreover, naloxone did not antagonize the decrease in neophobia observed after anxiolytic treatment in Balb/c mice in the free exploratory paradigm. In this strain, benzodiazepines produced an increase of locomotor activity, whereas naloxone decreased it. The stimulant effects of benzodiazepines on locomotor activity were abolished by naloxone. As naloxone (2 mg/kg) reversed the morphine-induced hyperthermia both in Swiss and in Balb/c mice, differences in possible pharmacokinetic factors between the two strains can be ruled out as an explanation for the failure of naloxone to antagonize anxiolytic-like effects in Balb/c mice. Therefore, the ability of naloxone to reverse anxiolytic effects does not hold for all strains of mice.

Topics: Animals; Anti-Anxiety Agents; Chlordiazepoxide; Diazepam; Exploratory Behavior; Fever; Male; Mice; Mice, Inbred BALB C; Morphine; Naloxone; Narcotic Antagonists; Narcotics

The dried aqueous extract of leaves of Buddleia cordata (loganiaceae) and its main flavonoid glycoside, linarin, have been evaluated for analgesic and antipyretic effects in mice and rats, respectively. Both the extract and linarin exerted significant and dose-dependent analgesic and antipyretic activities, the first being obtained against a chemical stimulus (writhing a test in mice) and the second being obtained by a pyretogenic stimulus (yeast-induced hyperthermia test). Furthermore, the response of the animals in the hot plate test was modified by linarin and an aqueous extract. These activities were similar to that showed by morphine sulfate (MS) and they were inhibited by naxolone pretreatment, a specific morphinic antagonist compound. These findings lead to the conclusion that the aqueous extract and linarin exert central analgesic properties. On the other hand, linarin was shown to be responsible for the antipyretic activity of this species.

Topics: Analgesics; Analgesics, Non-Narcotic; Animals; Fever; Glycosides; Male; Mice; Mice, Inbred Strains; Morphine; Naloxone; Pain; Plant Extracts; Plants, Medicinal; Rats; Rats, Wistar

Interferon-alpha (IFN-alpha, 2.0 x 10(4) units) was bilaterally microinjected into the medial preoptic area and anterior hypothalamus in conscious rats treated 10 min prior with an opioid receptor antagonist, naloxone (NLX, 2 mg/kg, IM) or a prostaglandin synthetase inhibitor, acetaminophen (ACAP, 25 mg/kg, IM). The IFN-alpha-induced rise of rectal temperature (Tre) was suppressed from 20 to 60 min in NLX pretreated rats and from 30 to 180 min in ACAP pretreated rats. The rate of rise in Tre during the initial 20 min observed in NLX pretreated rats was significantly smaller than that in ACAP or saline pretreated rats. ACAP suppressed the fever when it was given 50 or 100 min after injection of IFN-alpha. In contrast, NLX did not affect the fever when given 25 or 50 min after IFN-alpha. The results suggest that an opioid that its involvement may last only in the early phase of the fever, but not after the plateau has been reached.

Topics: Analysis of Variance; Animals; Arachidonic Acid; Fever; Interferon-alpha; Male; Microinjections; Naloxone; Rats; Rats, Wistar; Receptors, Opioid

In an attempt to examine the role of opioid system functioning in social attachment and isolation stress in young domestic fowl, the effects of morphine (5.0 mg/kg) and naloxone (5.0 mg/kg) were evaluated on distress vocalizations, thermal nociception, thermoregulation, and respiration following 15 min of isolation in 7-day-old White-Leghorn cockerels. Morphine decreased and naloxone increased distress vocalizations in isolated chicks. Isolation produced an increase in jump response latencies (i.e., hypoalgesia) on a standard hot-plate test. In general, morphine decreased and naloxone increased mean jump latencies in both isolated and nonisolated chicks. Isolation produced an increase in core body temperature (i.e., hyperthermia); morphine decreased and naloxone increased core body temperatures independent of the isolation manipulation. Social isolation did not affect respiration. However, morphine depressed respiration in both isolated and nonisolated chicks. These results support the notion that opioid systems modulate social attachment and isolation stress.

Topics: Analgesia; Animals; Chickens; Fever; Male; Morphine; Naloxone; Narcotics; Nociceptors; Pain Measurement; Respiration; Social Isolation; Stress, Psychological; Vocalization, Animal

We have previously shown that the febrile response of guinea pigs to lipopolysaccharide (LPS) is attenuated by the subcutaneous administration of the tertiary mu-receptor opioid antagonist naloxone-hydrochloride (Nal-HCl). Because Nal-HCl readily crosses the blood-brain barrier (BBB), this study was undertaken to investigate whether its effect on fever is mediated peripherally or centrally. For this, the effects of 1) Nal-HCl (23 and 46 mumol/kg sc), 2) the quaternary opioid antagonists Nal-methiodide (Nal-mI, 46 and 92 mumol/kg sc) and Nal-methobromide (Nal-mBr, 92 mumol/kg sc), which do not cross the BBB, and 3) intracerebroventricular Nal-HCl (0.25 and 1.25 mumol) on the febrile response to intravenous S. enteritidis LPS (2 micrograms/kg) were investigated in conscious guinea pigs. Under afebrile conditions, both Nal-HCl (whether administered sc or icv) and its quaternary analogues induced hypothermic responses. Peripheral Nal-HCl, Nal-mI, and Nal-mBr also attenuated both phases of the characteristically biphasic LPS fever. The thermal effects of the peripheral opioid antagonists, both tertiary and quaternary, were associated with cutaneous vasodilation. Intracerebroventricularly administered Nal-HCl did not evoke any attenuation of fever. The analysis of the data shows that Nal-HCl possesses three different thermoregulatory actions: a central hypothermic action, a peripheral thermolytic action (which is due to, at least partly, cutaneous vasodilation), and a peripheral antipyretic action. The latter effect suggests that, in guinea pigs, circulating opioids may have a role in fever production.

Topics: Animals; Blood-Brain Barrier; Body Temperature; Dose-Response Relationship, Drug; Fever; Guinea Pigs; Injections, Intraventricular; Injections, Subcutaneous; Lipopolysaccharides; Male; Naloxone; Skin Temperature

We investigated the humoral mechanisms involved in tumour necrosis factor alpha (TNF alpha)-induced fever in rabbits. No change in lymphocyte-activating factor activity was detected in serum drawn during TNF alpha-induced fever. The pyrogenic activity of recombinant rabbit interleukin-1 beta (IL-1 beta) was entirely abolished by pre-incubation with anti-IL-1 beta antiserum from the goat. Fever induced by intravenous (i.v.) injection of IL-1 beta was significantly diminished by i.v. infusion of the antiserum. However, i.v. infusion of the antiserum for 1 h did not affect fever induced by i.v. injection of TNF alpha, when the antiserum infusion began either simultaneously with, or 2 h after, the injection of TNF alpha. Furthermore, intracerebroventricular injection of the anti-serum did not affect TNF alpha-induced fever. The intracerebroventricular administration of naloxone (an opioid receptor antagonist) significantly diminished TNF alpha-induced fever. The results suggest that IL-1, both in the blood circulation and in the brain, may not be involved in TNF alpha-induced fever. Similar to the contribution of eicosanoids, the opioid system in the brain seems somehow to contribute to the mechanism of the development of fever induced by TNF alpha in rabbits.

Topics: Animals; Fever; Immune Sera; Interleukin-1; Male; Naloxone; Rabbits; Tumor Necrosis Factor-alpha

The effect of the opioid antagonist naloxone on the antipyretic action of acupuncture was studied in rabbits. Naloxone (0.1-0.2 mg/kg) when administered intravenously prior to acupuncture reduced the intensity and duration of the antipyretic action of acupuncture only in the initial stage. The data suggest participation of an endogenous opioid system in initiation of a number of responses mediating the antipyretic effect of acupuncture.

Topics: Acupuncture Therapy; Animals; Body Temperature; Fever; Male; Naloxone; Pyrogens; Rabbits

It was recently reported that the opiate antagonist, naloxone (Nal), blocks the changes induced by the endogenous pyrogen, interferon-alpha 2 (IFN), in the electrical activity of hypothalamic thermosensitive neurons in rat brain slice preparations. This study was undertaken to determine whether the pyrogenic response to this cytokine might, therefore, be modulated through Nal-reversible opiate receptors. To examine this possibility, conscious guinea pigs were injected IV with recombinant human (rh) IFN (10 MU/animal), or, for comparison, with S. enteritidis endotoxin (lipopolysaccharide, LPS; 2 micrograms/kg), rh tumor necrosis factor-alpha (TNF; 20 micrograms/kg), or rh interleukin-6 (IL6; 50 micrograms/kg); Nal (10 mg/kg, SC) was administered immediately before the pyrogens. And also for comparison, in separate experiments, indomethacin (Indo; 10 mg/kg, IM) was injected 20 min before the pyrogens. Both Nal and Indo abolished the febrile rises evoked by IFN, TNF, and IL6. Nal reduced the first and suppressed the second of the characteristically bimodal febrile response to LPS; Indo depressed both peaks. Neither blocker had any significant thermal effect by itself. These results suggest that two processes may mediate the pyrogenic effects of these substances, viz., an endogenous opioid- and a PGE-dependent mechanism.

Topics: Animals; Fever; Guinea Pigs; Indomethacin; Interleukin-6; Lipopolysaccharides; Male; Naloxone; Tumor Necrosis Factor-alpha

We have examined changes in rectal temperature of mice after subcutaneous administrations of d-methamphetamine alone or methamphetamine plus morphine. Methamphetamine 5 mg/kg produced slight hyperthermia, while simultaneous administration of morphine (25-100 mg/kg), which alone produces hypothermia, potentiated markedly the increase in body temperature by methamphetamine. Methamphetamine showed a hyperthermic effect in a dose-dependent manner in the presence of morphine. The hyperthermia due to methamphetamine plus morphine was avoided by pretreatment with 10 mg/kg naloxone. When animals were pretreated with 2.5 mg/kg haloperidol, hyperthermia due to methamphetamine alone was completely abolished, while that due to methamphetamine plus morphine was still observed. These results showed that dopamine may be implicated in methamphetamine hyperthermia and a haloperidol-nonsensitive mechanism may be involved in the methamphetamine-morphine hyperthermia.

Topics: Animals; Body Temperature Regulation; Drug Synergism; Fever; Haloperidol; Male; Methamphetamine; Mice; Morphine; Motor Activity; Naloxone

The non-specific opiate antagonist naloxone protects immature rats from hyperthermic seizures which occur when the animals are exposed to an environment of 40 degrees C and 55% humidity. Most of the currently used antiepileptic therapeutic agents can be said to contain either a hydantoin or a moiety stereochemically closely related to one. We have added a hydantoin group to naloxone and created a new combined chemical, naloxyl-6-alpha spirohydantoin. The new compound was ten times as effective as naloxone against hyperthermic seizures in 15-day old rat pups. Unlike naloxone, the new naloxone-hydantoin derivative retained a protective effect 24 hrs after injection.

Topics: Animals; Body Temperature; Environment, Controlled; Fever; Hydantoins; Hyperthermia, Induced; Naloxone; Rats; Rats, Inbred Strains; Seizures; Sodium Chloride

The role of skeletal muscle thermogenesis (increases in skeletal muscle tone) in the hyperthermic responses of conscious, unrestrained rats given acute or repeated i.p. or i.c.v. injections of morphine sulfate (MS) or beta-endorphin was investigated. Initial blood gas experiments showed that rats given acute i.p. injections of MS caused PO2 and pH to decrease by 60 min postadministration in a dose-related fashion whereas PCO2 increased; with repeated MS administration the respiratory acidosis seen with acute injections was reduced. Acute i.p. injections of MS (1, 10 or 20 mg/kg) caused catalepsy scores, plasma lactate levels and electromyographic (EMG) amplitude to be elevated in a dose-related fashion along with a rise in rectal temperatures (TRS). Surface (tail) temperatures also rose after the acute MS injections but only after the increase in TR. Significant increases in EMG amplitude after acute injections of MS occurred even before TRS increased and, with subsequent naloxone HCl administration (10 mg/kg i.p.), a rapid and marked fall in EMG amplitude occurred before TRS fell back to saline control levels. Acute i.c.v. injections of 1.1 nmol of either MS or beta-endorphin also caused EMG amplitudes to rise significantly before TRS began to increase. Tail temperatures again increased passively after i.c.v. injection of either drug. Subsequent naloxone injections (10 mg/kg i.p.) to these groups also caused EMG amplitudes to decrease before TRS decreased back to control TRS. Repeated i.p. injections of MS (10 mg/kg i.p. daily for 5 days) caused TRS to be higher than those seen after the initial injection but catalepsy scores, plasma lactates and EMG amplitudes were below those respective levels seen upon acute MS administration. Similar chronic findings occurred in other groups of rats given 1.1 nmol of either MS or beta-endorphin i.c.v., when they had been previously given repeated i.p. injections of MS (5 mg/kg i.p. twice daily for 2 days). The results indicate that acute peripheral or central injections of MS or beta-endorphin to conscious rats cause skeletal muscle to be activated, resulting in nonlocomotor, catatonic behavior. This skeletal muscle activation occurs before the rise in TR and is thought to be an important and possibly the primary cause of the resultant hyperthermia seen in rats after acute central or peripheral administration of MS or beta-endorphin. Repeated injections of morphine cause TRS to escalate higher, compared to that seen

Topics: Animals; beta-Endorphin; Body Temperature; Body Temperature Regulation; Electromyography; Fever; Male; Morphine; Muscles; Naloxone; Rats; Rats, Inbred Strains

Topics: Animals; Blood Pressure; Fever; Hot Temperature; Injections, Intraventricular; Naloxone; Pressoreceptors; Rabbits; Stress, Physiological

The effects of morphine sulfate on rectal temperature and on Ca++-stimulated Mg++ATPase activity in crude synaptosomal fraction (P2) of cortex, hypothalamus and cerebellum were investigated in rat. Morphine (3-15 mg/kg, SC) produced hyperthermia at 30-120 min after the drug administration. The Ca++/Mg++ ATPase activity in hypothalamus and cortex was decreased while there was no change in Mg++ ATPase activity. The enzyme activity in cerebellum was not affected. The opiate antagonist naloxone hydrochloride (5 mg/kg, SC) antagonized the effect of morphine on rectal temperature and Ca++/Mg++ ATPase activity. The effects of different calcium channel antagonists (nimodipine 1 mg/kg, verapamil 2.5 mg/kg and diltiazem 10 mg/kg, SC) on the changes induced by morphine were also investigated. These antagonists not only antagonized morphine hyperthermia, but also the inhibitory effect of morphine on Ca++/Mg++ ATPase activity in hypothalamus. The calcium channel agonist BAY K8644 (3 mg/kg, SC) produced hypothermia and also stimulation of Ca++/Mg++ ATPase activity in hypothalamus. Naloxone failed to alter these effects of BAY K8644. These studies demonstrate that Ca++ transport in hypothalamus, as indicated by Ca++/Mg++ ATPase activity, plays an important role in thermoregulation and thermoregulatory changes induced by opiates.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Biological Transport, Active; Body Temperature Regulation; Brain; Ca(2+) Mg(2+)-ATPase; Calcium; Calcium Channel Blockers; Calcium-Transporting ATPases; Fever; Male; Morphine; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid

The most common sign of febrile diseases is anorexia, which develops at a time when adequate caloric and micronutrient availability may be critical. In order to study the relationship of fever and anorexia, feed intake in dwarf goats was studied under conditions of fever and antipyresis. Furthermore, experiments were done to establish whether a feed intake stimulant would override the anorexia during febrile conditions. Infection with Ehrlichia phagocytophila and i.v. injection of Escherichia coli endotoxin (0(111) B4, 0.1 microgram/kg body weight) both resulted in increased rectal temperatures and significant reductions in feed intake. Administration of the antipyretic drug flurbiprofen (1 mg/kg) to febrile animals inhibited the temperature responses, but food intake was still suppressed. Diazepam (0.06 mg/kg), a feed intake stimulant, did not override the anorexia associated with fever. Blocking the febrile response of E. coli LPS-injected goats with flurbiprofen plus diazepam or with flurbiprofen plus naloxone (0.1 mg/kg) did not antagonise their reduced feed intake either. The effects of these drugs and of endotoxin on rumen motility adds an interesting aspect to their activities in the CNS, since the CNS has been shown to regulate various aspects of forestomach motility, which in turn could alter feeding behaviour. Moreover, our findings are consistent with the hypothesis that the suppression of feed intake might depend on the release of interleukin-1.

Topics: Animals; Anorexia; Diazepam; Drug Therapy, Combination; Eating; Ehrlichia; Endotoxins; Escherichia coli; Escherichia coli Infections; Female; Fever; Flurbiprofen; Goats; Male; Naloxone; Propionates; Rickettsiaceae Infections

Psychological stress results in a rise in body temperature. Here we report that in rats, hyperthermia induced by open-field stress can be blocked by administration of the antipyretic drug sodium salicylate. These data suggest that this rise in body temperature is a true fever, perhaps mediated by prostaglandins.

Topics: Animals; Fever; Male; Naloxone; Prostaglandins; Rats; Rats, Inbred Strains; Sodium Salicylate; Stress, Psychological

The effect of morphine injection into the midbrain periaqueductal gray (PAG) was examined on thermal response in rats. Rectal temperature (Tre) was recorded in unanesthetized and unrestrained animals before and after PAG morphine injection of 5 or 10 micrograms in cold (10 degrees C), neutral (22 degrees C), and hot (34 degrees C) environments. Both doses of morphine caused hyperthermia. Sixty to 105 min after the injection, Tre rose by 1.0-1.5 degrees C regardless of ambient temperature. Naloxone (2 mg/kg, i.p.) blocked the hyperthermic effects of morphine. Injection sites producing hyperthermia were distributed mostly in the ventral PAG and its ventral environs. The analgesic effect of morphine was examined by the tail-flick test. Locations of morphine injection effective for producing analgesia were restricted to the ventral area of the region responsible for hyperthermia. Magnitude of the hyperthermia did not significantly differ between animals with or without analgesia. The effect of PAG morphine (5 micrograms) was tested on tail vasomotor response to hypothalamic and scrotal thermal stimulations in urethane anesthetized (1.0 g/kg) animals. Threshold hypothalamic temperature for the vasodilation was lower at a scrotal temperature of 40 degrees C than at 30 degrees C. Following PAG morphine, threshold hypothalamic temperature rose and the difference in threshold hypothalamic temperature at the two scrotal temperatures disappeared.

Topics: Animals; Body Temperature; Fever; Male; Morphine; Naloxone; Periaqueductal Gray; Rats; Rats, Inbred Strains; Temperature; Vasodilation; Vasomotor System

Morphine action at opiate receptors in the ventral tegmental area (VTA) of the rat brain has been implicated in the production of increased locomotor activity and in morphine's rewarding properties. In the present experiments, bilateral administration of morphine (18 micrograms tapped into the tips of 28 gauge cannulae) into the VTA resulted in an increase in body temperature in rats. This effect was both reversed and blocked by a systemic injection of the opiate receptor blocker, naloxone, suggesting that it was due to morphine action at opiate receptors. The neuroleptic, pimozide, injected systemically four hours prior to morphine administration completely blocked the increased locomotor activity but had no effect on the hyperthermia. These data demonstrate that the hyperthermia was not brought about by the increased physical activity. Furthermore, these results suggest that while morphine-induced reward and increased locomotor activity may be mediated by an interaction of morphine and the ascending mesolimbic dopamine system, the hyperthermia is not. In an additional experiment, the effect of systemic injections of the central neurotransmitter receptor antagonists, scopolamine, phenoxybenzamine, and methergoline, on the hyperthermia induced by morphine in the VTA was investigated. Only the serotonin antagonist, methergoline, attenuated the hyperthermia.

Topics: Animals; Body Temperature Regulation; Fever; Male; Metergoline; Morphine; Motor Activity; Naloxone; Phenoxybenzamine; Pimozide; Rats; Rats, Inbred Strains; Receptors, Adrenergic; Receptors, Cholinergic; Receptors, Dopamine; Receptors, Serotonin; Scopolamine; Stereotaxic Techniques; Tegmentum Mesencephali

Rabbits were made febrile by an intravenous injection of homologous endogenous pyrogen (Interleukin 1). When naloxone (0.1 mg/kg i.v.) followed by 0.06 mg (kg X hr)-1 infusion) was given at the same time as the pyrogen, the resulting fever was indistinguishable from that following pyrogen alone. It appears unlikely that opioid receptors which are blocked by naloxone play an important part in the fever process.

Topics: Animals; beta-Endorphin; Body Temperature; Endorphins; Fever; Interleukin-1; Male; Naloxone; Pyrogens; Rabbits; Time Factors

Topics: Animals; Apomorphine; Body Temperature; Bromocriptine; Drug Interactions; Fever; Haloperidol; Male; Methotrimeprazine; Morphine; Naloxone; Rats; Rats, Inbred Strains; Rectum; Time Factors

The effects of endogenous hyperprolactinaemia (HPRL), as induced by pituitary homografts under the kidney capsule, on core temperature (Tc) was investigated in rats before and after the application of restraint stress. HPRL was accompanied by a significant decrease in Tc of freely moving rats, as observed for four days after pituitary homografts. HPRL-induced hypothermia was totally reversed by intraperitoneal (IP) injection of naloxone. In normoprolactinaemic (NPRL) rats, IP administration of naloxone caused a small but significant decrease in Tc and attenuated rise in temperature following the application of restraint stress. After application of restraint stress, Tc of HPRL rats raised to the level of unstressed NPRL rats. However, HRPL rats injected IP with naloxone showed no increase in Tc after restraint stress application. The effects of HPRL on Tc seem to involve an opioid component, and support the concept of a role played by stress hormones of hypophyseal origin in the control of Tc.

Topics: Animals; Body Temperature Regulation; Endorphins; Fever; Humans; Male; Naloxone; Prolactin; Rats; Rats, Inbred Strains; Restraint, Physical; Stress, Psychological; Synaptic Transmission

Meptazinol, a partial opioid agonist, diminishes the Jarisch-Herxheimer reaction in relapsing fever whereas naloxone, a pure opioid antagonist, is virtually inert. Because endogenous opioid activity is probably increased in the acute phase, the efficacy of meptazinol is unlikely to be due to agonist activity. However, it is possible that in such a severe reaction there may be an exhaustion of endogenous opioids, giving rise to a naturally occurring quasi-morphine-withdrawal syndrome which responds to meptazinol.

Topics: Anti-Bacterial Agents; Azepines; Body Temperature; Endorphins; Fever; Humans; Meptazinol; Models, Biological; Naloxone; Substance Withdrawal Syndrome; Syphilis

Discrete, bilateral, radiofrequency destruction of the ventral noradrenergic bundle (VB) resulted in a pronounced fall in levels of noradrenaline in the hypothalamus but not in the cortex. On days 4 and 12, but not 28, post-surgery, VB-lesioned rats were hyperactive (rearing and ambulation) upon exposure to a novel open-field space. This hyperactivity was greatly attenuated by naloxone, which did not significantly modify sham activity. These data suggest that the VB may be involved in the control of locomotor-exploratory activity via an interaction with an endorphinergic system. On day 4, but not 12 or 25, VB-lesioned rats displayed a significant elevation in core temperature (Tc). No difference in the hyperthermia elicited by introduction into the open-field was, however, seen between VB-lesioned and sham rats on day 4. In both groups, this rise in Tc was strongly attenuated by naloxone. These data indicate that the VB may be involved in the control of Tc but that it does not mediate novelty-stress evoked hyperthermia, for which endorphins are primarily responsible. Within 7 days post-surgery, VB-lesioned rats developed an enhancement of daily food intake which led to a slight obesity. From day 15 onward, a hyperdipsia was also seen in VB-lesioned rats. Naltrexone reduced the food and water intake of both sham and VB-lesioned animals but failed to totally block this hyperphagia. It is suggested that the VB is involved in the regulation of daily ingestive behaviour and that endorphins do not exclusively mediate the VB-lesion induced hyperphagia.

Topics: Afferent Pathways; Animals; Behavior, Animal; Body Temperature Regulation; Body Weight; Drinking; Eating; Endorphins; Feeding Behavior; Fever; Male; Medulla Oblongata; Naloxone; Norepinephrine; Pons; Rats; Rats, Inbred Strains; Time Factors

Morphine elicited a dose-related increase in the duration of phencyclidine (PCP)-induced motor incoordination. In the open field behavioral observations, morphine enhanced the PCP-induced decrease in the number of ambulation and rearing. Morphine potentiated the PCP-induced decrease in body temperature. The LD50 of PCP was significantly decreased in the presence of morphine. An opiate antagonist, naloxone, antagonized the morphine-induced effects without influencing the pharmacological actions of PCP itself. The levels of hepatic microsomal cytochrome P-450 and cytochrome b5 and the activities of NADPH dehydrogenase and NADPH cytochrome c reductase were unaffected by morphine treatment. The half-lives of PCP in serum and brain were increased by the concurrent administration of morphine. The ratio of the liver weight to body weight and aniline hydroxylase activity in hepatic microsomal fraction were decreased in the morphine-treated group compared with the control group; this is indicative of a possible reduction in the oxidative metabolism of PCP. The results indicate that acute administration of morphine enhances a variety of pharmacological effects of PCP; an inhibition of PCP disposition by morphine may be a mechanism involved in this process.

Topics: Aniline Compounds; Animals; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Drug Interactions; Drug Synergism; Fever; Half-Life; Hypothermia; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Microsomes, Liver; Morphine; Motor Activity; Naloxone; Phencyclidine

Intracerebroventricular administration of prototype non-peptide opioid receptor (mu, kappa, sigma) agonists, morphine, ketocyclazocine and N-allyl normetazocine (SKF 10,047) and an agonist at both kappa and sigma receptors, pentazocine, induced hyperthermia in guinea-pigs. Similar administration of peptide opioids like beta-endorphin (BE), methionine enkephalin (Met-E), leucine enkephalin (Leu-E) and their synthetic analogues D-ala2-methionine-enkephalinamide (D-ala2-Met-E) and D-ala2-leucine-enkephalinamide (D-ala2-Leu-E) also caused hyperthermia. Of the three anion transport systems (iodide, hippurate and liver-like) present in the choroid plexus, only the liver-like transport system seems to be important to central inactivation of beta-endorphin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin since iodipamide (an inhibitor of the liver-like transport system) augmented the hyperthermia. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide- and non-peptide opioid-induced hyperthermia because a prostaglandin synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to administration of peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine and beta-endorphin since naloxone attenuated the effect. In contrast, the hyperthermic responses to ketocyclazocine, SKF 10,047, pentazocine, Met-enkephalin, Leu-enkephalin, D-ala2-Met-enkephalin and D-ala2-Leu-enkephalin were not antagonized by naloxone. Lack of antagonism of naloxone on pyrogen, arachidonic acid, PGE2, dibutyryl cAMP and NE-induced hyperthermia indicates that endogenous opioid peptides are not likely to be central mediators of the hyperthermia induced by these agents.

Topics: Animals; Body Temperature; Endorphins; Fever; Guinea Pigs; Indomethacin; Iodipamide; Naloxone; Narcotics; Norepinephrine; Phenoxybenzamine; Theophylline

Rats were given a single unilateral microinjection of B-endorphin in the periaqueductal gray, followed by a second microinjection of the same dose of B-endorphin in the same site a week later. A decrease in the analgesic action (i.e., tolerance) but an increase in the hyperthermic action (i.e., sensitization) was observed over this interval. These results suggest that different receptors may mediate these actions of B-endorphin. In addition, these results indicate the need for caution in repeated-measurements studies using this opiate peptide, since the assumption that such temporal effects dissipate within 3-5 days, with resulting minimal carry-over effects from the preceding treatment appears to be unjustified.

Topics: Analgesia; Analgesics; Animals; beta-Endorphin; Body Temperature; Cerebral Aqueduct; Drug Tolerance; Endorphins; Fever; Male; Naloxone; Rats; Rats, Inbred Strains; Receptors, Opioid; Time Factors

Potency of analgetic activity of SL-573 was between that of indomethacin and aminopyrine in chemical stimulation tests. The analgetic activity of SL-573 was 3.2 times as potent as that of aminopyrine in the phenylquinone writhing test, 4.1 times as potent as aminopyrine in the acetic acid writhing test and 6.3 times as potent as aminopyrine in the Randall and Selitto test. Thus the analgetic activity of SL-573 appears to be comparable etic to that of codeine. SL-573, unlike narcotic analgesics, showed common properties to known antipyretic analgesics and anti-inflammatory agents in the following points. (1) Analgetic activity was not evident in the mechanical stimulation or in the heat stimulation tests. (2) The analgetic activity was not antagonized by naloxone. (3) SL-573 showed no antagonistic effect to morphine. (4) Tolerance to the analgetic activity of SL-573 was not observed after a one week pretreatment with this compound. (5) SL-573 had no effect on the evoked potentials recorded from cells in the pain pathway of CNS and the site of action of analgetic effect was considered to be in peripheral sites of the sensory neurons. The antipyretic activity of SL-573 was equal to that of aminopyrine in febrile rabbits and 4 times as potent as that of aminopyrine in febrile rats. This compound did not affect normal body temperature of rabbits and rats, this observation being similar to that noted with antipyretic analgesics and nonsteroidal anti-inflammatory agents.

Topics: Afferent Pathways; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Binding Sites; Body Temperature; Dose-Response Relationship, Drug; Drug Tolerance; Evoked Potentials; Fever; Male; Mice; Morphine; Naloxone; Physical Stimulation; Quinazolines; Quinazolinones; Rabbits; Rats; Stimulation, Chemical; Typhoid-Paratyphoid Vaccines; Yeast, Dried

Topics: Animals; Endorphins; Fever; Humans; Male; Naloxone; Rats; Stress, Psychological