naloxone and Amnesia

Evidence is discussed which points to the existence of a physiologic amnesic mechanism mediated by beta-endorphin and perhaps by other opioid peptides as well. This mechanism is triggered by various forms of training and by either painful or painless stimulation. It may operate through the inhibition of central dopaminergic and beta-adrenergic systems that modulate the memory consolidation process. This amnesic mechanism in unrelated to the regulation of pain perception, and operates at opioid peptide levels several orders of magnitude below those that are needed to cause analgesia or other effects. In addition, shuttle avoidance and habituation learning seem to be dependent on a state induced by the release of beta-endorphin. It is possible that this may be related to the amnesic properties of this substance. Therefore, it appears that the endogenous opioid peptides may exert their primary function in the modulation of memory processes.

Topics: Amnesia; Animals; beta-Endorphin; Brain; Dopamine; Dose-Response Relationship, Drug; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Humans; Learning; Memory; Naloxone; Naltrexone; Norepinephrine; Rats

The opiate antagonist naloxone has been reported to improve memory in animals and to produce partial improvement in Alzheimer's dementia. The usefulness of naloxone for reversing ECT-induced cognitive impairment was tested by comparing the effects of naloxone and placebo on several tests of cognitive performance in 10 patients who underwent bilateral ECT. No significant differences were found between naloxone and placebo. The results suggest that at the doses used, naloxone is not effective in reversing ECT-induced memory deficits.

Topics: Adult; Aged; Amnesia; Cognition Disorders; Depressive Disorder; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Naloxone; Psychological Tests

Topics: Adult; Aged; Amnesia; Cognition Disorders; Electroconvulsive Therapy; Female; Humans; Male; Middle Aged; Naloxone; Neurocognitive Disorders; Orientation; Psychological Tests

Bile duct ligation (BDL) induces primary biliary cirrhosis characterized by cholestasis, impaired liver function and cognition including impairment of memory formation and anxiety-like behaviors. Endogenous opioid and acetylcholine levels are elevated in animal model of cholestasis. In addition, there is no data about the effects of interaction opioidergic and cholinergic systems of dorsal hippocampus (CA1) on amnesia-induced by cholestasis. Male mice weighing 25-35 g were used in this study. Cholestasis was induced by the ligation of the common bile duct. One-trial step-down and hole-board paradigms were used for the assessment of memory retrieval and anxiety-like behaviors respectively. All drugs injected intra-CA1. The data showed that cholestasis (24 days after BDL) decreased memory retrieval. Sole intra-CA1 injection of higher dose of mecamylamine (0.125, 0.25, 0.5 and 1 μg/mice) and scopolamine (0.125, 0.25, 0.5 1 and 2 μg/mice) but not all doses of naloxone (0.0125, 0.025 and 0.05 μg/mice) decreased memory retrieval in the sham operated BDL. The ineffective doses of naloxone (0.025 and 0.05 μg/mice), mecamylamine (0.5 μg/mice) and scopolamine (0.5 μg/mice) restored cholestasis-induced amnesia 24 days after BDL. Further, all cross co-administration ineffective doses of naloxone (0.0125 μg/mice), mecamylamine (0.125 μg/mice) and scopolamine (0.125 μg/mice) reversed cholestasis-induced amnesia. All doses of the drugs have no effect on exploratory behaviors. The data strongly revealed that synergistic effect between opioidergic and cholinergic systems of CA1 on the modulation of cholestasis-induced amnesia.

Topics: Amnesia; Animals; Animals, Outbred Strains; CA1 Region, Hippocampal; Cholestasis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Exploratory Behavior; Male; Mecamylamine; Mental Recall; Mice; Microinjections; Muscarinic Antagonists; Naloxone; Narcotic Antagonists; Nicotinic Antagonists; Receptors, Opioid; Scopolamine

Previous exposure to the training context disrupts glutamatergic N-methyl-d-aspartate receptor (NMDAr) antagonist-induced amnesia, indicating that novelty is necessary for such an amnestic effect. While there are reports that novelty-related release of opioids cause amnesia, no study has addressed whether the amnestic effect of NMDAr antagonists involve opioid mechanisms. In this study we investigated whether pharmacological manipulation of the opioid system immediately after context pre-exposure alters the amnestic effect of arcaine, a NMDAr antagonist. Adult male Wistar rats were habituated (pre-exposed) to a fear conditioning training apparatus or to a different context (open field). Immediately after pre-exposure, animals were injected with saline or naloxone (0.5 mg/kg, i.p.) or anti-beta-endorphin antibody (1:500, i.c.v.). Forty eight hours after pre-exposure session, all animals were subjected to fear conditioning acquisition protocol and saline or arcaine (30 mg/kg, i.p.) was administered immediately after training. Testing was carried out 24 h later, and freezing responses due to re-exposure to the training apparatus were recorded. Pre-exposure to the training apparatus prevented the impairment of memory induced by post-training arcaine. Administration of naloxone or anti-beta-endorphin antibody, immediately after pre-exposure to the training apparatus, reinstated the amnesic effect of post-training arcaine. The results suggest that endogenous opioid mechanisms are involved in the pre-exposure-induced loss of the amnestic effect of arcaine.

Topics: Amnesia; Animals; Association Learning; Biguanides; Conditioning, Psychological; Fear; Freezing Reaction, Cataleptic; Male; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Opioid, mu

The present study investigated the effect of morphine sensitization on the impairment of spatial memory retrieval induced by acute morphine in adult male rats. Spatial memory was assessed by 2-day Morris water maze task which included training and test day. On the training day, rats were trained by a single training session of 8 trials. On the test day, a probe trial consisting of 60s free swim period without a platform and the visible test were administered. Morphine sensitization was induced by subcutaneous (s.c.) injection of morphine, once daily for 3 days followed by 5 days without drug treatment before training. The results indicated that acute administration of morphine (7.5mg/kg, s.c.) before testing impaired spatial memory on the test day. Pre-test morphine-induced amnesia decreased in morphine-sensitized (15 and 20mg/kg, s.c.) rats. Improvement in spatial memory retrieval in morphine-sensitized rats was inhibited by once daily administration of naloxone (1 and 2mg/kg, s.c.) 30 min prior to the injection of morphine for three days. The results suggest that morphine sensitization reverses the impairment of spatial memory retrieval induced by acute morphine and it is implied that mu-opioid receptors may play an important role in this effect.

Topics: Amnesia; Analgesics, Opioid; Animals; Behavior, Animal; Central Nervous System Sensitization; Dose-Response Relationship, Drug; Male; Maze Learning; Memory; Mental Recall; Morphine; Naloxone; Narcotic Antagonists; Nerve Tissue Proteins; Neurons; Rats; Rats, Wistar; Receptors, Opioid, mu; Spatial Behavior; Swimming

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

The authors examined the role of the endogenous opioid system in infantile amnesia for contextual fear conditioning. Rats that were 18 days of age received an aversive footshock in a novel context. Rats displayed conditioned fear when tested 1 min after training but not 24 hr after training. Systemic injection of the opioid receptor antagonist naloxone prior to test, but not immediately after training, alleviated infantile amnesia. Naloxone also alleviated infantile amnesia when injected prior to test 7 days after training. These effects of naloxone were due to actions on central rather than peripheral opioid receptors and were not due to any tendency of the drug to produce fear or freezing. These results show that central opioid receptors regulate retrieval of fear memories in infant rats.

Topics: Amnesia; Animals; Animals, Newborn; Conditioning, Psychological; Disease Models, Animal; Dose-Response Relationship, Drug; Fear; Female; Freezing Reaction, Cataleptic; Male; Memory; Naloxone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Retention, Psychology; Time Factors

Electroconvulsive shock (ECS) applied immediately after passive avoidance learning in rats caused partial amnesia. This could be prevented by administering r-ANP into the lateral brain ventricle. The effects of pre-treatment with different receptor blockers: (haloperidol, atropine, phenoxybenzamine, propranolol, naloxone, bicuculline and methysergide) on the ANP-induced antiamnesia were investigated. The receptor blockers per se in the doses selected had no influence on the ECS-induced amnesia. Haloperidol, atropine and propranolol blocked the antiamnestic action of the peptide, while phenoxybenzamine, naloxone, bicuculline and methysergide were ineffective. The results confirm our previous observations that ANP might play a role in learning and memory processes and also suggest that the antiamnestic action of the peptide is mediated by dopaminergic, cholinergic and beta-adrenergic mediator systems.

Topics: Amnesia; Animals; Atrial Natriuretic Factor; Atropine; Avoidance Learning; Bicuculline; Electroshock; Haloperidol; Male; Memory; Methysergide; Naloxone; Phenoxybenzamine; Propranolol; Rats

Amnesia produced by scopolamine and cycloheximide were reversed by morphine given 30 min before the test trial (pre-test), and pre-test morphine also facilitated the memory retrieval in the animals administered naloxone during the training trial. Similarly, pre-test scopolamine partially reversed the scopolamine-induced amnesia, but not significantly; and pre-test cycloheximide failed to reverse the cycloheximide-induced amnesia. These results suggest that the facilitation of memory retrieval by pre-test morphine might be the direct action of morphine rather than a state dependent effect.

Topics: Amnesia; Animals; Avoidance Learning; Cycloheximide; Male; Memory; Mice; Morphine; Naloxone; Premedication; Scopolamine; Time Factors

It has been established in experiments on male mice and rats that caerulein antagonized the behavioural effects of ketamine, an agonist of phencyclidine receptors. Caerulein (75-375 micrograms/kg) and haloperidol (0.1-1.5 mg/kg) suppressed the stereotyped behaviour and motor excitation induced by ketamine (30 mg/kg) in mice. Caerulein and haloperidol failed to affect ketamine-induced ataxia. Caerulein (10 micrograms/kg) and the opioid antagonist naloxone (5 mg/kg) completely blocked the amnestic action of ketamine (30 mg/kg) in passive avoidance experiments on rats. It seems likely that the suppression of the behavioural effects of ketamine by caerulein is related to its functional antagonism with dopamine and opioid receptors.

Topics: Amnesia; Animals; Ataxia; Behavior, Animal; Ceruletide; Haloperidol; Ketamine; Male; Mice; Motor Activity; Naloxone; Rats; Receptors, Cholecystokinin; Stereotyped Behavior

The effects of cholecystokinin octapeptide (CCK-8), cholecystokinin tetrapeptide amide (CCK-4), beta-endorphin, proglumide, and naloxone on passive avoidance behavior were studied in rats. Intracerebroventricular (i.c.v.) injection of beta-endorphin (1-10 micrograms) had no significant influence on the latency of the avoidance response in intact rats. Also, beta-endorphin (0.05-5 micrograms, i.c.v.) did not affect the response in rats treated with electroconvulsive shock (ECS). The preventive effect of CCK-8 (0.1-1.0 micrograms, i.c.v.) on ECS-induced amnesia was partly antagonized by beta-endorphin (0.05-10 micrograms, i.c.v.). Intraperitoneal (i.p.) injection of naloxone (1-10 mg/kg) could not prevent ECS-induced amnesia, but continuous subcutaneous infusion of this drug (2 mg/day, 7 days) completely abolished the amnesia. Naloxone (1 and 10 mg/kg, i.p.) also partly antagonized amnesia induced by proglumide (1 and 10 micrograms, i.c.v.) and prevented it when induced by CCK-4 (5 and 10 micrograms, i.c.v.). The results indicate the facilitating action of naloxone and the inhibitory effect of beta-endorphin on memory, suggesting that the endogenous opiate systems are involved in some way in the memory processes.

Topics: Amnesia; Animals; Avoidance Learning; beta-Endorphin; Cholecystokinin; Electroshock; Injections, Intraperitoneal; Injections, Intraventricular; Male; Naloxone; Proglumide; Rats; Rats, Inbred Strains

The amnesia induced by cycloheximide (CXM) injected SC and by CXM or anisomycin injected ICV immediately after the training test was antagonized in combination with an opiate antagonist, naloxone (NLX). This antagonism occurred on both the passive avoidance- and escape-learning responses in a dose-dependent manner in mice. NLX alone (0.3-10.0 mg/kg) did not alter the performances of these tasks. Furthermore, the decrease in retention performance on shuttle avoidance in rats induced by CXM was also antagonized by NLX. Treatment with CXM and/or NLX did not affect spontaneous locomotor activity. The interaction of these drugs on the performance of the passive avoidance- and escape-learning and the shuttle avoidance tasks may be related to neurochemical memory processes. These results suggest that an opioid system may participate in the amnesic actions induced by protein synthesis inhibitors in these models.

Topics: Amnesia; Animals; Anisomycin; Avoidance Learning; Cycloheximide; Escape Reaction; Male; Memory; Mice; Naloxone; Pyrrolidines; Rats; Rats, Inbred Strains

Mice were trained in a 1-trial inhibitory avoidance task (0.7 mA FS) and tested for retention at 1, 3, or 6 h following training. Posttraining beta-endorphin (0.1 micrograms/mouse i.p.) administration impaired retention at 6 h, but not 1 or 3 h after training. Propranolol (0.3 mg/mouse i.p.), but not naloxone (0.1 mg/mouse i.p.) administered prior to retention testing at 1 or 3 h accelerated the onset of amnesia in mice given posttraining beta-endorphin. Neither propranolol nor naloxone affected retention when given alone. These findings suggest that the delayed onset of the amnesia produced by posttraining beta-endorphin is due to the activation of a beta-adrenergic system.

Topics: Amnesia; Animals; beta-Endorphin; Endorphins; Male; Memory; Mice; Naloxone; Propranolol; Receptors, Adrenergic, beta; Retention, Psychology; Time Factors

This study investigated the effect of naloxone on amnesia produced by subseizure amygdaloid stimulation. Animals were trained in an inhibitory avoidance task, and given amygdaloid stimulation following training. Immediately after training, prior to stimulation, naloxone was injected either peripherally (i.p.) or into the bed nucleus of the stria terminalis (BNST) where the Met-enkephalin-containing fibers from the amygdala terminate. Amygdaloid stimulation caused retention deficits. The deficits were attenuated by 3.0 mg/kg naloxone given peripherally or by 1.0 microgram or 0.3 microgram naloxone injected bilaterally into the BNST. The attenuative effect was anatomically and receptor specific: 0.3 microgram of naloxone injected into the caudate nucleus was ineffective; the attenuative effect of naloxone was antagonized by simultaneous injection of 1.5 or 4.5 micrograms levorphanol into the BNST. These results suggest that endogenous opioids, possibly the enkephalins of the stria terminalis released into the BNST following amygdaloid stimulation, are at least partially involved in mediating the effect of amygdaloid stimulation on memory.

Topics: Amnesia; Amygdala; Animals; Avoidance Learning; Electric Stimulation; Humans; Male; Naloxone; Rats; Rats, Inbred Strains; Seizures

Immediate post-training i.p. injection of Met-enkephalin, Leu-enkephalin or des-Tyr-Met-enkephalin, caused retrograde amnesia for a shuttle avoidance task in rats. The effect was linearly related to the log of the dose between 0.32 and 2.0 microgram/kg, and the potency of the three compounds was similar (ED50 0.35-0.45 microgram/kg). Naloxone (0.2 mg/kg) antagonized the amnestic effect of the peptides. Since the log dose-response curves were displaced to the right in quasi-parallel fashion, and Lineweaver-Burk plots of the data showed an intersection very close to the origin of the horizontal axis, the antagonism between naloxone and the three peptides appears to be competitive.

Topics: Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; Drug Antagonism; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Female; Humans; Kinetics; Naloxone; Rats

Topics: Acid-Base Equilibrium; Adult; Amnesia; Anesthesia, Intravenous; Blood Flow Velocity; Blood Glucose; Blood Pressure; Carbon Dioxide; Cardiovascular System; Central Venous Pressure; Heart Rate; Humans; Lactates; Male; Morphine; Naloxone; Nitrous Oxide; Oxygen; Oxygen Consumption; Pyruvates; Respiration; Unconsciousness; Vascular Resistance