naloxone and Memory-Disorders

Based on its unique pharmacological profile, buprenorphine may produce less impairment in psychomotor and cognitive performance than methadone. However, the few studies that have investigated the performance effects of buprenorphine in opioid-abusing volunteers examined effects of single acute doses rather than effects of repeated dosing and included a very limited range of measures. The present inpatient study evaluated dose-related effects of repeated administration of the buprenorphine/naloxone combination product (8/2, 16/4, 32/8 mg, sublingual tablets) in eight opioid-dependent volunteers on performance of a broad range of tasks, following a period of 7-10 days of dosing at each level, in a double-blind, within-subject, crossover design. The testing battery included measures of psychomotor speed, time perception, conceptual flexibility, focused attention, working memory, long-term/episodic memory, and metamemory. Supporting the hypothesis of limited impairment with buprenorphine, results revealed minimal impairment in performance as buprenorphine/naloxone dose was increased four-fold. The only significant effect of dose was an impairment in episodic/long-term memory (recognition memory) performance at the highest dose (32/8 mg) relative to the two lower doses. Future studies incorporating larger sample sizes and non-drug controls, as well as directly comparing buprenorphine to methadone and LAAM are needed to further test the hypothesis of limited impairment with buprenorphine.

Topics: Adult; Buprenorphine; Cognition Disorders; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Male; Memory Disorders; Naloxone; Narcotic Antagonists; Neuropsychological Tests; Opioid-Related Disorders; Psychomotor Disorders

Pulpal pain is a common orofacial health issue that has been linked to cognitive impairment. Because of its prominent role in pain modulation and cognitive impairment, apelin (Apl) is regarded as a promising target for clinical pain management. The role of Apl in orofacial pain, however, is unknown. The purpose of this study was to determine the effects of intra-periaqueductal grey matter (PAG) administrations of Apl-13 on capsaicin-evoked pulpal nocifensive behaviour and capsaicin-induced spatial learning and memory impairments in rats.. Forty-nine male Wistar rats (200-250 g) were randomly divided into seven groups (n = 7 per group). The groups included: untreated intact, capsaicin (Caps) only, three Caps+Apl groups that received different dosages of intra-PAG injection of Apl-13 (1, 2 and 3 μg/rat) 20 min prior to capsaicin application, and two Apl+antagonist groups that received Apl receptor antagonist or naloxone (a μ opioid receptor) 20 min before Apl injection. Learning and memory were assessed using the Morris water maze test. One-way analysis of variance followed by Tukey post hoc tests was used for statistical analysis.. Intra-PAG administration of Apl-13 significantly reduced the capsaicin-induced nocifensive behaviour (p < .01). This antinociception effect was inhibited by F13A and naloxone. Apl-13 inhibited nociception-induced learning and memory deficits (p < .01). The cognitive effects were also blocked by pre-treatment administration of F13A (3 μg/rat).. These findings indicated that Apl-13, via Apl receptors (AR or APJ) and μ opioid receptors, alleviated capsaicin-induced dental nocifensive behaviour and protected against nociception-induced learning and memory impairments. As a result of our findings, Apl appears to be a promising analgesic option for further research in orofacial pain models and clinical trials.

Topics: Animals; Apelin; Capsaicin; Facial Pain; Male; Memory Disorders; Naloxone; Periaqueductal Gray; Rats; Rats, Wistar; Spatial Learning

Drug addiction is a chronic disorder resulted from complex interaction of genetic, environmental, and developmental factors. Epigenetic mechanisms play an important role in the development and maintenance of addiction and also memory formation in the brain. We have examined passive avoidance memory and morphine conditioned place preference (CPP) in the offspring of male and/or female rats with a history of adulthood morphine consumption. Adult male and female animals received chronic oral morphine for 21days and then were maintained drug free for 10days. After that, they were let to mate with either an abstinent or control rat. Male offspring's memory was evaluated by step through test. Besides, rewarding effects of morphine were checked with CCP paradigm. Offspring of abstinent animals showed significant memory impairment compared to the control group which was more prominent in the offspring of abstinent females. Conditioning results showed that administration of a high dose of morphine (10mg/kg) that could significantly induce CPP in control rats, was not able to induce similar results in the offspring of morphine abstinent parents; and CPP was much more prominent when it was induced in the offspring of morphine exposed females compared to the progeny of morphine exposed males. It is concluded that parental morphine consumption in adulthood even before mating has destructive effects on memory state of the male offspring and also leads to tolerance to the rewarding effects of morphine. These effects are greater when the morphine consumer parent is the female one.

Topics: Analysis of Variance; Animals; Avoidance Learning; Conditioning, Operant; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Male; Memory Disorders; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Sex Factors; Substance Abuse, Oral

In the present study, we investigated the effects of microinjection of vitamin B

Topics: Analgesics; Animals; CA1 Region, Hippocampal; Catheters, Indwelling; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Facial Pain; Formaldehyde; Male; Maze Learning; Memory Disorders; Microinjections; Motor Activity; Naloxone; Narcotic Antagonists; Nootropic Agents; Rats, Wistar; Scopolamine; Vibrissae; Vitamin B 12

The neuroprotective role of the endogenous opioid system in the pathophysiological sequelae of brain injury remains largely ambiguous. Noteworthy, almost no data is available on how its genetically determined activity influences the outcome of mild traumatic brain injury. Thus, the aim of our study was to examine the effect of opioid receptor blockage on cognitive impairments produced by mild traumatic brain injury in mice selectively bred for high (HA) and low (LA) swim-stress induced analgesia that show innate divergence in opioid system activity. Mild traumatic brain injury was induced with a weight-drop device on anaesthetized mice. Naloxone (5mg/kg) was intraperitoneally delivered twice a day for 7days to non-selectively block opioid receptors. Spatial memory performance and manifestations of depressive-like behavior were assessed using the Morris Water Maze and tail suspension tests, respectively. Mild traumatic brain injury resulted in a significant deterioration of spatial memory performance and severity of depressive-like behavior in the LA mouse line as opposed to HA mice. Opioid receptor blockage with naloxone unmasked cognitive deficits in HA mice but was without effect in the LA line. The results suggest a protective role of genetically predetermined enhanced opioid system activity in suppression of mild brain trauma-induced cognitive impairments. Mice selected for high and low swim stress-induced analgesia might therefore be a useful model to study the involvement of the opioid system in the pathophysiology and neurological outcome of traumatic brain injury.

Topics: Analgesia; Animals; Behavior, Animal; Brain Concussion; Depression; Disease Models, Animal; Male; Memory Disorders; Mice; Mice, Inbred Strains; Naloxone; Narcotic Antagonists; Neuroprotection; Receptors, Opioid; Spatial Memory; Up-Regulation

A growing body of evidence suggests that the agglomeration of amyloid-β (Aβ) may be a trigger for Alzheimer׳s disease (AD). Central infusion of Aβ42 can lead to memory impairment in mice. Inhibiting the aggregation of Aβ has been considered a therapeutic strategy for AD. Endomorphin-1 (EM-1), an endogenous agonist of μ-opioid receptors, has been shown to inhibit the aggregation of Aβ in vitro. In the present study, we investigated whether EM-1 could alleviate the memory-impairing effects of Aβ42 in mice using novel object recognition (NOR) and object location recognition (OLR) tasks. We showed that co-administration of EM-1 was able to ameliorate Aβ42-induced amnesia in the lateral ventricle and the hippocampus, and these effects could not be inhibited by naloxone, an antagonist of μ-opioid receptors. Infusion of EM-1 or naloxone separately into the lateral ventricle had no influence on memory in the tasks. These results suggested that EM-1 might be effective as a drug for AD preventative treatment by inhibiting Aβ aggregation directly as a molecular modifier.

Topics: Amyloid beta-Peptides; Analgesics, Opioid; Animals; Infusions, Intraventricular; Male; Memory Disorders; Mice; Naloxone; Narcotic Antagonists; Oligopeptides; Peptide Fragments; Psychomotor Performance; Receptors, Opioid, mu; Recognition, Psychology

The aim of the present study was to investigate the effect of swimming exercise on elevated plus-maze (EPM)-associated memory deficit induced by intra-CA1 injection of scopolamine (a muscarinic acetylcholine receptor antagonist used to model Alzheimer's disease in rodents) in male mice. In addition, involvement of the mu opioid receptors in this phenomenon was investigated.. Bilateral guide cannulae were implanted to allow intra-CA1 microinjections.. Data showed that mice with 10 and 20 days of swimming, only acquired the emotional memory, while 30 days of swimming exercise improved it. On the other hand, pretest intra-CA1 injection of scopolamine at the doses of 2 and 3 but not 1 μg/mouse reduced the emotional memory. Our results demonstrated that 20 days of swimming by itself and without any drug injection restored the emotional memory deficit induced by intra-CA1 injection of scopolamine, only at the dose of 2 but not 3 μg/mouse. Moreover, once daily injection of the subthreshold doses of morphine (2.5 and 5 mg/kg, i.p.) during the last 7 days of the 20 day-swimming intervention, improved the emotional memory deficit induced by scopolamine (3 μg/mouse) and this effect could be blocked by the subthreshold doses of naloxone (0.2 and 0.4 mg/kg). It was noted that all previous interventions did not alter the anxiety-like behaviors.. Swimming improved the emotional memory by itself and restored the emotional memory deficit induced by the intra-CA1 injection of scopolamine. Mu opioid receptor-dependent mechanism(s) is(are) suggested to play a role in this phenomenon.

Topics: Animals; Emotions; Exploratory Behavior; Male; Memory Disorders; Mice; Morphine; Naloxone; Physical Exertion; Receptors, Opioid, mu; Scopolamine; Swimming

Bile duct ligation (BDL) is an animal model used in cholestatic disease research. Both opioidergic and nitrergic systems are known to be involved in cholestasis. The aim of this study was to investigate the possible interaction between these two systems in BDL-induced memory formation and exploratory behaviors in mice. Male mice weighing 25-30 g were divided into nonoperated controls, sham-operated, and BDL groups. One-trial step-down and hole-board paradigms were used to assess memory acquisition and exploratory behaviors, respectively. Cholestasis did not alter memory acquisition while increasing exploratory behaviors 7 days after BDL. A pretraining intraperitoneal injection of L-arginine (50, 100, and 200 mg/kg), L-NG-nitroarginine methyl ester (L-NAME) (5, 10, 20, and 40 mg/kg), or naloxone (0.125, 0.25, and 0.5 mg/kg) did not alter memory acquisition or exploratory behaviors, whereas morphine (5 and 7.5 mg/kg) decreased memory acquisition in sham-operated animals. Moreover, although injection of L-NAME and naloxone exerted no effect on memory acquisition in the 7 days post-BDL mice, L-arginine (100 and 200 mg/kg) and morphine (2.5, 5, and 7.5 mg/kg) injection reduced it. In contrast, L-NAME and naloxone, but not morphine or L-arginine, reduced the BDL-induced exploratory behaviors. Coadministration of subthreshold doses of morphine (1.25 mg/kg) and L-arginine (50 mg/kg) caused a memory deficit in 7 days post-BDL mice. However, the memory deficit induced by the effective doses of morphine (2.5 mg/kg) or L-arginine (200 mg/kg) in these mice was restored by the administration of either naloxone (0.5 mg/kg) or L-NAME (40 mg/kg). In addition, naloxone and L-NAME reduced the exploratory behaviors in L-arginine-pretreated mice but not in morphine-pretreated mice. We conclude that there appears to be a synergistic effect between opioidergic and nitrergic systems on memory acquisition and exploratory behaviors in cholestatic mice.

Topics: Analgesics, Opioid; Animals; Arginine; Avoidance Learning; Cholestasis; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Exploratory Behavior; Ligation; Male; Memory Disorders; Mice; Morphine; Naloxone; Narcotic Antagonists; NG-Nitroarginine Methyl Ester; Nitric Oxide

In the present study, we investigated the effects of repeated morphine pre-treatment on impairment of spatial memory acquisition induced by intra dorsal hippocampus (intra-CA1) administration of the non-selective cannabinoid CB1/CB2 receptor agonist, WIN55,212-2 in adult male rats. 2-day version of Morris water maze task has been used for the assessment of spatial memory. On the training day, rats were trained by a single training session of eight trials and 24 h later a probe trial test consist of 60s free swim period without a platform and the visible test was administered. Animals received pre-treatment subcutaneous (s.c.) injections of morphine, once daily for three days followed by five days drug-free treatment before training trials. The results indicated that bilateral pre-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) impaired acquisition of spatial memory on the training and test day. The amnesic effect of WIN55, 212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (20 mg/kg/day × 3 days, s.c.). Improvement in spatial memory acquisition in morphine-pretreated rats was inhibited by once daily administration of naloxone (1 and 2 mg/kg, s.c.) 15 min prior to injection of morphine for three days. The results suggest that sub-chronic morphine treatment may produced sensitization to cannabinoids, which in turn reversed the impairment of spatial memory acquisition induced by WIN55,212-2 and mu- opioid receptors may play an important role in this effect.

Topics: Animals; Benzoxazines; CA1 Region, Hippocampal; Discrimination, Psychological; Male; Maze Learning; Memory Disorders; Morphine; Morpholines; Naloxone; Naphthalenes; Narcotic Antagonists; Narcotics; Psychotropic Drugs; Rats, Wistar; Spatial Memory; Task Performance and Analysis; Time Factors; Visual Perception

Recent studies show that morphine possesses protective preconditioning effects in different ischemia/reperfusion models. However, there is very little information about the antineuroinflammatory role of morphine and its protective effect against memory deficit. In the present study, we evaluated the role of morphine preconditioning in a model of mild neuroinflammation induced by intraperitoneal lipopolysaccharide (LPS) injection (1 mg/kg). Rats were trained on passive avoidance apparatus and challenged with LPS 20 h later. Four hours after LPS, rats were subjected to passive avoidance testing and then for the assessments of inflammatory and apoptotic cell death mediators in the hippocampus. LPS significantly increased the nuclear NF-κB and expression of COX-2, IL-1β, and TNF-α, augmented the activity of caspase-3 and PARP cleavage, and in parallel shortened the latencies to enter the dark compartment. Although morphine injection in a noninflammatory context was able to induce a neuroinflammatory response and memory loss, morphine preconditioning at the dose of 4 mg/kg significantly prevented the LPS-induced neuroinflammation and memory deficit. Morphine preconditioning was abolished by naloxone and, therefore, is dependent on opioid receptors. These results suggest that acute morphine injection, in spite of the induction of a neuroinflammatory response and amnesia per se, exerts an antineuroinflammatory role and protects from cell death and memory deficit in an inflammatory context.

Topics: Analgesics, Opioid; Animals; Avoidance Learning; Brain Ischemia; Caspase 3; Encephalitis; Ischemic Preconditioning; Lipopolysaccharides; Male; Memory Disorders; Morphine; Naloxone; Narcotic Antagonists; Neuroprotective Agents; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerases; Random Allocation; Rats; Rats, Wistar; Receptors, Opioid

Morphine withdrawal leads to the activation of endocannabinoid system and cognitive deficits. The aim of this study was to evaluate the effects of AM281, a cannabinoid antagonist/inverse agonist, on memory deficit following naloxone-precipitated morphine withdrawal in mice. Male mice were made dependent by increasing doses of morphine (30-90 mg/kg) twice daily for 3 days. The object recognition task was used to evaluate memory dysfunction. The test comprised three sections: habituation for 15 min., first trial for 12 min. and test trial for 5 min. In this learning paradigm, the difference in exploration between a previously seen object and a new object is taken as an index of memory performance (recognition index). The recognition index was assessed on the third day of morphine treatment by the injection of 0.1 mg/kg naloxone 3 hr after the last dose of morphine. Chronic administration of AM281 at 2.5 mg/kg significantly improved the memory impairment, producing a recognition index of 36.0 ± 3.9 as compared with vehicle-treated data (recognition index = -3.1 ± 8.2%). A single dose of AM281 at 5 mg/kg improved the recognition index from -1.5 ± 3.9% in morphine withdrawal animals to 18.5 ± 11.6%. Concurrent administration of AM281 with morphine proved to be more effective in protecting the animals from losing their memory compared to acute action of AM281. These results indicate that the contribution of the cannabinoid system to memory deficit is attributable to morphine withdrawal. By blocking cannabinoid receptors, AM281 may become useful in preventing memory deficit after morphine withdrawal.

Topics: Animals; Cannabinoids; Male; Memory Disorders; Mice; Morphine; Morpholines; Naloxone; Pyrazoles; Receptor, Cannabinoid, CB1; Recognition, Psychology; Substance Withdrawal Syndrome

In the present study, the effects of morphine treatment upon reduction of memory consolidation by post-training administration of the non-selective cannabinoid CB(1)/CB(2) receptor agonist, WIN55,212-2, into the dorsal hippocampus (intra-CA1) have been investigated in rats. Step-through inhibitory avoidance apparatus was used to test memory retrieval, which was made of two white and dark compartments. In training day, electric shocks were delivered to the grid floor of the dark compartment. On the test day, the animal was placed in the white compartment and allowed to enter the dark compartment. The latency with which the animal crossed into the dark compartment was recorded as memory retrieval. Morphine was injected subcutaneously (S.C.), once daily for three days, followed by a five day morphine-free period before training. Bilateral post-training intra-CA1 infusions of WIN55,212-2 (0.25 and 0.5 μg/rat) shortened the step-through latency, which suggested impaired memory consolidation. The deleterious effect of WIN55,212-2 (0.5 μg/rat) was prevented in rats previously injected with morphine (10 mg/kg/day × 3 days, S.C.). Prevention of the WIN55,212-2-induced amnesic-like effect was counteracted by the mu-receptor antagonist, naloxone, and the dopamine D(2) receptor antagonist, sulpiride, but not by the D(1) receptor antagonist, SCH 23390, when administered prior to each morphine injection. The results have suggested that subchronic morphine treatment may cause mu-opioid and D(2) receptor sensitization, which in turn prevents impairment of memory consolidation induced by WIN55,212-2.

Topics: Amnesia; Analgesics; Animals; Avoidance Learning; Benzazepines; Benzoxazines; CA1 Region, Hippocampal; Dopamine Antagonists; Dopamine D2 Receptor Antagonists; Male; Memory; Memory Disorders; Morphine; Morpholines; Naloxone; Naphthalenes; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; Receptors, Dopamine D1; Receptors, Opioid, mu; Sulpiride; Time Factors

Glucocorticoid hormones evidently affect memory. Morphine withdrawal causes a cognitive deficit and an increase in corticosterone secretion. In the present study brain corticosterone concentrations were determined after morphine withdrawal. Male mice were made dependent by increasing doses of morphine over 3 days. Blood and brain samples were collected following withdrawal induced by injection of naloxone (0.1 mg/kg) or spontaneously after 4 and 14 h. Brain corticosterone was extracted and measured by enzyme immunoassay. Short-term memory was determined in the novel object recognition task, using a 20 min interval between the learning trial and the test trial. In this memory trial, the difference in exploration between a previously seen object and a novel object is taken as an index of memory performance (recognition index, RI). RI in morphine dependent mice undergoing withdrawal was decreased compared to their control group. Brain corticosterone concentrations after naloxone withdrawal or 4 h after spontaneous withdrawal were respectively 22 and 34% greater than control values. Corticosterone concentration was normalized 14 h after the last dose of morphine. The results indicate that increase in brain corticosterone concentration may play an important role in short-term memory impairment following morphine withdrawal.

Topics: Animals; Brain; Corticosterone; Male; Memory Disorders; Memory, Short-Term; Mice; Morphine; Naloxone; Recognition, Psychology; Substance Withdrawal Syndrome

The opiate-receptor antagonist naloxone was administered to rats after passive-avoidance training either alone or in combination with forced-swim stress. A retention test revealed that while naloxone enhanced retention when administered alone, it impaired retention when administered in combination with forced-swim stress. The findings provide evidence for a "protective" endogenous opioid-based system that, when not blocked pharmacologically, limits enhancement or impairment of retention under conditions of mild and intense stress, respectively.

Topics: Analysis of Variance; Animals; Avoidance Learning; Electroshock; Male; Memory; Memory Disorders; Naloxone; Narcotic Antagonists; Neuropsychological Tests; Random Allocation; Rats; Rats, Long-Evans; Stress, Psychological; Swimming; Time Factors

In the present study, effects of intracerebroventricular (i.c.v.) injections of mu-opioid receptor agonist and antagonist on lithium state-dependency were investigated. For memory assessment, a one-trial step-down inhibitory avoidance task was used in adult male NMRI mice. Intraperitoneal (i.p.) administration of lithium (10 mg/kg) after training impaired memory when retrieval was tested 24 h later. The memory impairment was reversed by pretest administration of the same dose of lithium, suggesting state-dependency induced by lithium. In addition, i.c.v. administration of both lithium (2 and 4 microg/mouse, i.c.v.) and morphine (3 and 6 microg/mouse, i.c.v.) before the test reversed memory impairment induced by post-training lithium (10 mg/kg, i.p.). On the other hand, pretest administration of naloxone (1 and 2 mg/kg) which had no effects alone on inhibitory avoidance response, prevented the improving effects of both morphine (3 microg/mouse, i.c.v.) and lithium (2 microg/mouse, i.c.v.) on memory retrieval. The results suggest that the mu-opioid receptors in the central nervous system may be involved in the retrieval of lithium state-dependent learning.

Topics: Animals; Antimanic Agents; Avoidance Learning; Lithium Chloride; Male; Memory Disorders; Mice; Morphine; Naloxone; Receptors, Opioid, mu

Physiological stress is known to produce analgesia and memory disruption. A large body of evidence favors the nonopiate mediation of stress-induced analgesia. It is suggested that brain histamine mediates nonopiate analgesia and participates in learning and memory in rodents. Histamine is released during stress, although the nature of histaminergic involvement in stress response is not clearly defined. Therefore, we studied the effect of L-histidine and histamine-receptor antagonists on antinociception and impaired retention induced by immobilization stress. In the present study, immobilization stress produced a naloxone-resistant analgesia that was potentiated by L-histidine and antagonized by pretreatment with the histamine receptor antagonists chlorpheniramine and cimetidine. L-histidine attenuated the memory disruption induced by immobilization stress, which was significantly reversed by chlorpheniramine but not by cimetidine. Thus the involvement of the central histaminergic system, through histamine H1- and H2-receptors, may be speculated in analgesia and cognitive deficit induced by immobilization stress.

Topics: Analgesia; Analgesics; Animals; Chlorpheniramine; Cimetidine; Cognition Disorders; Female; Histamine Agents; Histamine H1 Antagonists; Histamine H2 Antagonists; Histamine Release; Histidine; Male; Maze Learning; Memory Disorders; Mice; Naloxone; Narcotic Antagonists; Receptors, Histamine; Receptors, Histamine H1; Receptors, Histamine H2; Stress, Physiological

The effects of morphine and morphine withdrawal on memory performance were examined in mice by using Morris water maze task. Morphine-induced memory impairment at the doses of 5 and 10 mg/kg recovered after repeated administration. Oxotremorine, a muscarinic receptor agonist, at the dose of 0.1 mg/kg ip, and physostigmine, a cholinesterase inhibitor, at the dose of 0.1 mg/kg ip, significantly antagonized morphine (10 mg/kg sc)-induced memory impairment in mice. Furthermore, repeated naloxone (0.5 mg/kg ip) attenuated scopolamine (0.2 mg/kg ip)-induced memory impairment. By using escalating doses of morphine for 13 days, morphine-induced memory impairment was continuously maintained. When withdrawal was precipitated by naloxone (5 mg/kg ip), or administration of oxotremorine (0.1 and 0.2 mg/kg ip) or physostigmine (0.05 and 0.1 mg/kg ip), the impairment was completely reversed. These results suggest that morphine-induced memory impairment could be partially due to the inhibition of the central cholinergic activity.

Topics: Animals; Cholinergic Antagonists; Dose-Response Relationship, Drug; Injections, Subcutaneous; Male; Maze Learning; Memory Disorders; Mice; Morphine; Motivation; Muscarinic Agonists; Muscarinic Antagonists; Naloxone; Narcotic Antagonists; Narcotics; Oxotremorine; Parasympathetic Nervous System; Physostigmine; Scopolamine; Substance Withdrawal Syndrome

The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.

Topics: Analgesics, Opioid; Animals; Brain; Dose-Response Relationship, Drug; Drug Interactions; Male; Maze Learning; Memory Disorders; Memory, Short-Term; Mice; Muscarinic Antagonists; Naloxone; Naltrexone; Narcotic Antagonists; Neurons; Oligopeptides; Receptors, Opioid, mu; Scopolamine

The effects of fmol doses of nociceptin/orphanin FQ on scopolamine-induced impairment of learning and/or memory were examined using spontaneous alternation of Y-maze and step-down type passive avoidance tasks. While fmol doses of nociceptin alone had no effect on spontaneous alternation or passive avoidance behavior in normal mice, administration of nociceptin (10 and/or 100 fmol/mouse) 30 min before spontaneous alternation performance or the training session of the passive avoidance task, significantly improved the scopolamine-induced impairment of spontaneous alternation and passive avoidance behavior. This ameliorating effect was not antagonized by nocistatin (0.5 and 5.0 nmol/mouse, i.c.v.), naloxone benzoylhydrazone (2.3, 11.2, and 56.1 micromol/kg, s.c.) or nor-binaltorphimine (4.9 nmol/mouse, i.c.v.). These results indicated that very low doses of nociceptin ameliorate impairments of spontaneous alternation and passive avoidance induced by scopolamine, and suggested that this peptide has bidirectional modulatory effects on learning and memory; impairment at high doses and amelioration at low doses.

Topics: Analgesics, Opioid; Animals; Avoidance Learning; Disease Models, Animal; Dizocilpine Maleate; Learning Disabilities; Male; Maze Learning; Memory Disorders; Mice; Naloxone; Naltrexone; Narcotic Antagonists; Neuroprotective Agents; Nociceptin; Opioid Peptides; Psychomotor Performance; Rats; Scopolamine

An 8-arm radial maze task was used to assess the possible role of the opiate system in the spatial memory of the rat. Increasing doses of etonitazene (0.005-0.06 mg/kg i.p.) and morphine (2.5-100 mg/kg i.p.) significantly impaired performance in the working memory components of the task. For both drugs this impairment was linearly related to the log of the administered dose, and the log-dose relationships were parallel. The regression lines calculated for each parameter for both drugs were parallel thus allowing us to calculate the potency: etonitazene proved to about 1000 times more potent than morphine in terms of correct arm entries, the number of errors and the total time taken to complete the task. Moreover, the progressive cognitive impairment produced by both opiates was closely related to an increase in analgesic effect. Pretreatment with naloxone (5 mg/kg i.p.) completely antagonised the disruptive effect of the opiates on working memory. The importance of the mu subtype opiate receptor in cognitive processes is discussed.

Topics: Analgesia; Animals; Benzimidazoles; Catalepsy; Male; Maze Learning; Memory Disorders; Morphine; Naloxone; Narcotics; Rats; Rats, Wistar; Receptors, Opioid, mu

Acute exposure of rats to microwaves (12.6 chr, 2375 MHz, power density 1 mW/cm2) induced the retrograde amnesia. It was show the role of opioidergic, benzodiazepine, GABAergic and cholinergic components in the amnesic effects of microwaves. Piracetam (100 mg/kg, i. p.) and oxiracetam (10 mg/kg, i. p.) prevented the negative effects of microwaves on memory processes.

Topics: Animals; Learning Disabilities; Male; Memory Disorders; Microwaves; Naloxone; Piracetam; Psychotropic Drugs; Pyrrolidines; Radioligand Assay; Rats; Rats, Wistar; Receptors, Cholinergic; Receptors, GABA-A; Receptors, Opioid

In a first set of experiments, immediately post-training morphine (1.0 or 2.5 but not 0.5 mg/kg) treatment, or immobilization stress (30 or 60 but not 15 min) impaired memory processes of non-pretrained DBA/2 mice tested in a passive avoidance box. The effects were naloxone-reversible and time-dependent (they were absent in mice injected with morphine, or immobilized, starting 120 min after training). No effect was evident in no-footshock groups injected with morphine (2.5 mg/kg) or immobilized (60 min), thus showing lack of proactive influence of the treatments on performance. In a second set of experiments, in which pretrained animals were used, both morphine and immobilization stress were less effective in disrupting memory processes of mice. In both sets of experiments a per se ineffective stress enhanced the effects of morphine. A number of possible hypotheses concerning the results obtained are examined. In particular the possible role of emotional factors in the effects of morphine on memory is discussed.

Topics: Animals; Avoidance Learning; Humans; Male; Memory Disorders; Mice; Mice, Inbred DBA; Morphine; Naloxone; Restraint, Physical; Stress, Psychological