Pharmacological evidence of a central effect of naltrexone, morphine, and beta-endorphin and a peripheral effect of met- and leu-enkephalin on retention of an inhibitory response in mice.
Immediate post-training administration of the central acting opioid receptor antagonist naltrexone (0.01-1.00 mg/kg) facilitated 48-h retention of a one-trial inhibitory avoidance task. An inverted-U dose-response curve was obtained. In this dose range naltrexone did not significantly affect response latencies of mice not given a footshock during the training. However, higher doses of naltrexone (3.0 and 10.0 mg/kg) increased latencies of both shocked and unshocked mice. The peripheral-acting opioid receptor blocker, naltrexone methyl bromide (MR 2263) (0.01-10.00 mg/kg), did not significantly influence retention latencies of either shocked or unshocked mice. Further, MR 2263 (0.1, 1.0, or 10.0 mg/kg) did not block the retention impairment produced by concurrently administered morphine (3.0 mg/kg) or beta-endorphin (0.1 microgram/kg). These findings indicate that the effect of these agonists on memory are not due to a peripheral influence. However, MR 2263 does prevent the memory-impairing effect of both metenkephalin (1.0 microgram/kg) and leu-enkephalin (0.3 microgram/kg) on retention. Those results suggest that enkephalins affect retention through influences initiated peripherally. Thus, different sites and mechanisms of action for beta-endorphin and the enkephalins are proposed.
D000313:Adrenal Medulla / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology; D004744:Enkephalin, Methionine / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds; D012153:Retention, Psychology / Q000187:drug effects / Q000502:physiology*; D001615:beta-Endorphin
D004723:Endorphins; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D009271:Naltrexone; D001615:beta-Endorphin; D009020:Morphine