beta-endorphin and Fever

Topics: Animals; beta-Endorphin; Body Temperature; Body Temperature Regulation; Dose-Response Relationship, Drug; Drug Tolerance; Endorphins; Enkephalin, Methionine; Fever; Hypothermia; Mice; Morphine; Narcotic Antagonists; Narcotics; Rats; Receptors, Opioid; Temperature

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

Heat stroke is characterized by hyperthermia, arterial hypotension, decreased baroreflex sensitivity, and increased serum levels of beta-endorphin. Whereas naltrexone may have therapeutic potential in heat stroke, the underlying mechanism remains unclear. We tested the hypothesis that naltrexone may attenuate heat stroke by reducing hyperthermia, hypotension, decreased baroreceptor sensitivity, and/or increased serum levels of beta-endorphin. Heat stroke was induced by exposing the anesthetized adult Sprague-Dawley rats in an incubator at 43 degrees C. The moment in which the mean arterial pressure dropped irreversibly from the peak level was taken as the onset of heat stroke. Control rats were exposed to 24 degrees C. Mean arterial pressure, baroreceptor sensitivity, and maximal reflex bradycardia, after the onset of heat stroke, were all significantly lower than in control rats. However, rectal temperature and serum levels of beta-endorphin were all greater after the onset of heat stroke. Intravenous delivery of naltrexone (10 mg/kg) 20 min before the initiation of heat stress, but not immediately at the onset of heat stroke, significantly attenuated the above-mentioned reactions. Accordingly, naltrexone improved survival during heat stroke. These results suggest that naltrexone protects against hypotension and decrement of both baroreceptor sensitivity and maximal reflex bradycardia during heat stroke by reducing both hyperthermia and increment of serum beta-endorphin and thus improves survival.

Topics: Animals; beta-Endorphin; Blood Pressure; Fever; Heart Rate; Heat Stroke; Hypotension; Male; Naltrexone; Narcotic Antagonists; Pressoreceptors; Rats; Rats, Sprague-Dawley

At first, we investigated whether both beta-endorphin release level in the hypothalamus and body temperature can be altered after intracerebroventricular (i.c.v.) injection of either lipopolysaccharide (LPS), interleukin-1beta (IL-1beta), or prostaglandin E(2) (PGE(2)) in rats. It was found that in the rat, i.c.v. administration of either LPS (0.5 microg in 10 microl), IL-1beta (10 ng in 10 microl), or PGE(2) (200 ng in 10 microl), in addition to producing fever, upregulated the immunoreactivity of beta-endorphin in the preoptic anterior hypothalamus of rat brain. Secondarily, we assessed whether the fever induced by either LPS, IL-1beta, or PGE(2) can be altered by pretreatment with buprenorphine (an opioid receptor antagonist). The results revealed that i.c.v. administration of buprenorphine (1 - 10 microg in 10 microl) alone had an insignificant effect on the body temperature. However, the fever induced by i.c.v. injection of either LPS, IL-1beta, or PGE(2) was significantly attenuated by pretreatment with i.c.v. injection of buprenorphine 1 h before the pyrogen injection in rats. The results suggest that pyrogens enhance beta-endorphin release in the hypothalamus and trigger fever which can be attenuated by buprenorphine, an opioid receptor antagonist.

Topics: Animals; beta-Endorphin; Buprenorphine; Dinoprostone; Fever; Hypothalamus; Immunohistochemistry; Injections, Intraventricular; Interleukin-1; Lipopolysaccharides; Male; Narcotic Antagonists; Pyrogens; Rats; Rats, Sprague-Dawley

Topics: Animals; beta-Endorphin; Fever; Interleukin-1; Male; Microinjections; Preoptic Area; Rats; Rats, Sprague-Dawley

This paper discusses the role of endogenous opioids in response to hyperthermia and the alterations observed in drug or alcohol addicts. Endorphins, rather than enkephalins are involved in adaptation to heat in the central nervous system. The pituitary secretion of beta endorphin together with ACTH in response to thermal stress provided the opportunity to measure the opioid reactivity to hyperthermia in health and toxicomania, as an index of opioid function, in adaptation to heat. The review of the data in the literature shows absent responses of beta endorphin and its related hormone ACTH to the thermal stress of sauna in heroin, cocaine or alcohol addicts. A common explanation for this phenomenon is that the long-term stimulation of hypothalamic opioid neurotransmission that is produced directly or indirectly by heroin, alcohol or cocaine, disrupts the opioid response to thermal stress, and thus the adaptation to heat.

Topics: Adrenocorticotropic Hormone; Alcoholism; beta-Endorphin; Cocaine; Fever; Healthy Worker Effect; Heroin Dependence; Hot Temperature; Humans; Male; Stress, Physiological; Substance-Related Disorders

In order to establish possible different reactions between normal subjects and cocaine addicts to short term exposure to heat, thermal, cardiovascular and pituitary hormonal responses to hyperthermia in sauna were measured in 8 male cocaine addicts (studied after 14 days of abstinence) and in 8 age and weight matched normal men. Subjects sat for 30 min in a sauna room, where the temperature was 90 C and the relative humidity 10%. Physiological and hormonal parameters were measured just before and after sauna and after 30 min of rest at normal (21 C) room temperature. Significant and comparable increments in systolic and diastolic blood pressure, pulse rate and sublingual temperature were observed in the two groups at the end of sauna. All these parameters decreased to normal values after 30 min of rest at normal room temperature. Before sauna, ACTH, cortisol and beta-endorphin levels were similar in the two groups, whereas plasma prolactin concentrations were significantly higher in cocaine addicts. All examined hormones rose significantly in the normal controls at the end of sauna. All hormones, except cortisol, returned to the basal levels after 30 min at normal room temperature. In contrast, no significant hormonal responses to hyperthermia were observed at any time point in cocaine addicts. These data do not provide evidence of alterations in the cardiovascular and thermal adaptive responses to hyperthermia in cocaine abusers. On the other hand, the results show an impairment of the ACTH/cortisol, beta-endorphin and prolactin responses to hyperthermia in cocaine addicts.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; beta-Endorphin; Blood Pressure; Body Temperature; Cocaine; Fever; Heart Rate; Humans; Hydrocortisone; Male; Prolactin; Steam Bath; Substance-Related Disorders

To evaluate the responses of circulating beta-endorphin, met-enkephalin and ACTH to sauna-induced hyperthermia, 8 male heroin addicts recently admitted to a therapeutic community and 8 age-matched normal subjects were examined. Compared with control subjects, heroin addicts showed 1. A decrease of the basal levels of beta-endorphin; 2. Absence of the normal increase of beta-endorphin and ACTH after sauna; 3. A lower increase in systolic blood pressure. It is concluded that an impairment of the adaptive response to stress may be present in heroin addicts, even after a relatively short drug-free period (14 days).

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Body Temperature Regulation; Enkephalin, Methionine; Fever; Hemodynamics; Heroin Dependence; Humans; Male; Steam Bath

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

The effects of pretreatment of rats with an intrahypothalamic injection of 6-hydroxydopamine on the thermal responses induced by intrahypothalamic injection of noradrenaline, prostaglandin E2, thyrotropin-releasing hormone or beta-endorphin were assessed. Administration of either noradrenaline (2-10 micrograms), prostaglandin E2 (10-40 ng), thyrotropin-releasing hormone (0.5-2.0 micrograms) or beta-endorphin (1-3 micrograms) into the preoptic anterior hypothalamus caused a dose-dependent rise in rectal temperature in conscious rats at an ambient temperature of 22 degrees C. In addition, it was found that three intrahypothalamic doses of 10 micrograms of 6-hydroxydopamine at intervals of 2 days caused a significant depletion of noradrenaline in the hypothalamus to 26.4% of control while the concentration of dopamine in the hypothalamus was not significantly reduced at 95.3% of control. Furthermore, the hyperthermic responses induced by prostaglandin E2, thyrotropin-releasing hormone, or beta-endorphin were greatly attenuated after selective depletion of noradrenaline in the hypothalamus in rats. However, selective depletion of noradrenaline did not affect the noradrenaline-induced hyperthermic responses. The data indicate that either prostaglandin E2, thyrotropin-releasing hormone or beta-endorphin may act through the endogenous release of noradrenaline from the hypothalamus to induce hyperthermic responses in rats.

Topics: Animals; beta-Endorphin; Dinoprostone; Dopamine; Endorphins; Fever; Hydroxydopamines; Hypothalamus; Male; Norepinephrine; Oxidopamine; Prostaglandins E; Rats; Rats, Inbred Strains; Thyrotropin-Releasing Hormone

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Body Temperature; Endorphins; Fever; Hot Temperature; Humans; Hydrocortisone; Male; Steam Bath

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

I.c.v. administration of bacterial endotoxin produced a fever in the Long-Evans rat but not in the Brattleboro rat. Similar administration of arachidonic acid, prostaglandin E2, prostacyclin, dibutyryl cAMP, norepinephrine, morphine and beta-endorphin caused hyperthermia in both Long-Evans and Brattleboro rats. Variable doses of exogenous arginine vasopressin (AVP) when centrally administered with endotoxin caused fever in the Brattleboro rat. It is suggested that AVP may play an important role in the production and release of endogenous pyrogen.

Topics: Animals; Arachidonic Acid; Arachidonic Acids; Arginine Vasopressin; beta-Endorphin; Body Temperature; Bucladesine; Dinoprostone; Endorphins; Endotoxins; Epoprostenol; Fever; Male; Morphine; Norepinephrine; Prostaglandins E; Rats; Rats, Brattleboro

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

Methergoline, an antagonist of cerebral serotonin receptors, has been shown to significantly reduce the rise in rectal temperature (Tre) produced by the intracerebral microinjection of beta-endorphin. In this study the role of serotonin in the increase in Tre elicited by beta-endorphin was further examined using three additional serotonin antagonists. beta-Endorphin was administered twice to rats using a crossover design in which half of the animals were first pretreated with the vehicle solution and half with the antagonist. Serotonin antagonists used were: methergoline, methysergide, cinanserin and cyproheptadine. Although methergoline did cause a marked reduction in the beta-endorphin-induced rise in Tre, neither methysergide, nor cinanserin, nor cyproheptadine produced a marked reduction in the hyperthermia. Since methergoline also interacts with the dopamine receptor, the effect of a dopamine antagonist, haloperidol, on the endorphin-evoked response was also examined. Haloperidol failed to attenuate the rise in Tre. The reason for the apparent discrepancy in the action of these serotonin antagonists is unclear. Further research may reveal distinct subpopulations of serotonin receptors at which these antagonists exert differential effects.

Topics: Animals; beta-Endorphin; Body Temperature; Body Temperature Regulation; Cinanserin; Endorphins; Fever; Haloperidol; Metergoline; Methysergide; Rats; Serotonin Antagonists

Effects of intravenous beta-endorphin on body temperature and body weight loss were studied in naive and morphine-dependent mice. beta-Endorphin at doses 2.6-25.5 mg/kg injected intravenously caused hyperthermia in naive mice as well as in morphine-dependent mice. In addition, beta-endorphin and morphine reduced body-weight loss during the morphine withdrawal.

Topics: Animals; beta-Endorphin; Body Temperature; Body Weight; Drug Interactions; Endorphins; Fever; Injections, Intravenous; Male; Mice; Morphine