beta-endorphin 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 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

Posttraining administration of the opioid peptides, beta-endorphin or the enkephalins, is known to cause retrograde amnesia for a variety of tasks in rats. The present paper studies the effect of the posttraining administration of dynorphin 1-13 on retention of a step-down inhibitory avoidance task and of a shuttle avoidance task. For the purpose of comparison, the effect of human beta-endorphin was also studied. In confirmation of previous results, beta-endorphin (1.0 or 10.0 micrograms/kg, IP) caused retrograde amnesia for the two tasks. Dynorphin 1-13 had no effect at doses between 0.008-125.0 micrograms/kg IP or 1.25-125.0 ng/rat ICV in the inhibitory avoidance task, or at doses of 5.0, 25.0, or 125.0 micrograms/kg in the shuttle avoidance paradigm. These findings suggest that, in contrast to beta-endorphin, dynorphin 1-13 may not be involved in memory regulation at the posttraining period in rats.

Topics: Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; beta-Endorphin; Dynorphins; Endorphins; Female; Injections, Intraperitoneal; Injections, Intraventricular; Narcotics; Peptide Fragments; 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

The post-training amnestic effect of ACTH, beta-endorphin, adrenaline or tyramine on a step-down inhibitory avoidance task in rats was reversed by the administration of the same drugs prior to testing. Each drug was more effective as an anti-amnestic agent when the amnesia was induced by post-training administration of the same drug than of one of the others. alpha 2-Adrenergic receptors were shown to be involved in the amnestic and anti-amnestic actions of all the drugs and alpha 1 receptors to be involved in the anti-amnestic action of adrenaline and tyramine. These findings support the concept that memory depends on the relationship between the neurohumoral and hormonal states both after training and at the time of testing. These drugs would have limited value as contextual cues, and the mechanisms sensitive to their influence should be those involved in the availability of stored information for retrieval.

Topics: Adrenocorticotropic Hormone; Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; beta-Endorphin; Endorphins; Epinephrine; Female; Humans; Male; Rats; Rats, Inbred Strains; Tyramine

The ip administration of ACTH1-24 (0.2 microgram/kg) or adrenaline-HCl (5.0 micrograms/kg) immediately after training or 6 min prior to testing facilitated retrieval of a one-trial step-down inhibitory avoidance task in rats, acquired using a low intensity footshock. Post-training administration of beta-endorphin (0.1 micrograms/kg, ip) caused retrograde amnesia, but pre-test administration facilitated retrieval. The amnesia caused by post-training administration of beta-endorphin was prevented by ACTH, adrenaline or beta-endorphin given prior to testing. Memory facilitation was most pronounced when the same drug was administered both after the training session and prior to testing. These findings suggest that ACTH, adrenaline and beta-endorphin have at least two effects on memory processing: 1) during the post-training period on the entry of recently stored information into a system that makes it available for retrieval; and 2) both after training and during the test session, that makes learning dependent on states induced by the drugs.

Topics: Adrenocorticotropic Hormone; Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; beta-Endorphin; Endorphins; Epinephrine; Female; Humans; Memory; Rats; Rats, Inbred Strains

The intracerebroventricular (icv) administration of 5.0 or 25.0 ng of beta-endorphin or Met-enkephalin causes retrograde amnesia for a shuttle avoidance task ion rats. In both cases, the higher dose was more effective than the lower one. The present results confirm previous similar findings obtained using systemic administrations of these compounds, and suggest that the amnestic effect of beta-endorphin and Met-enkephalin is mediated centrally.

Topics: Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; beta-Endorphin; Dose-Response Relationship, Drug; Endorphins; Enkephalin, Methionine; Enkephalins; Female; Humans; Injections, Intraventricular; Rats; Rats, Inbred Strains

The endogenous opiate peptide, beta-endorphin (0.4, 1.0, 2.0, and 10.0 microgram/kg) was injected IP into rats immediately after training in a shuttle avoidance task, and its effect on memory retention was evaluated in test sessions carried out 24 h later. The drug was found to cause retrograde amnesia, the ED50 being 1.0 microgram/kg. Beta-endorphin immunoreactivity was measured in the hypothalamus and rest of the brain of rats submitted to training, or test sessions of shuttle avoidance learning, pseudoconditioning in the shuttle-box, tones alone, or foot-shocks alone. After training in any of the four paradigms, there was a marked (46-60%) depletion of beta-endorphin immunoreactivity in the rest of the brain. No changes were detected in the hypothalamus or after test sessions. The loss of beta-endorphin immunoreactivity may be attributed to release of this substance caused by the stimuli used for training. From the present findings, as well as previous observations on the memory-facilitating influence of the opiate receptor antagonist, naloxone, it is concluded that there is a physiological amnesic mechanism mediated by beta-endorphin (and perhaps other opoid peptides as well), which is triggered by the non-associative factors present in the various forms of learning.

Topics: Amnesia; Amnesia, Retrograde; Animals; Avoidance Learning; beta-Endorphin; Brain; Conditioning, Operant; Electric Stimulation; Endorphins; Female; Humans; Hypothalamus; Learning; Rats