The impairment of retention induced by beta-endorphin in mice may be mediated by a reduction of central cholinergic activity.

beta-Endorphin (0.03 to 1.00 microgram/kg, ip) impaired retention of a one-trial inhibitory avoidance task in a dose-dependent manner when injected into male Swiss mice immediately post-training, as indicated by retention performance 48 h later. The doses of 0.03 and 0.10 microgram/kg significantly impaired retention while the two higher doses (0.30 and 1.00 microgram/kg) did not significantly affect retention as compared with the control group, but tended to increase retention as compared with the dose of 0.10 microgram/kg. Thus, the dose-response curve shows an U-shaped form. The simultaneous injection of naloxone (0.1 mg/kg, ip) not only shifted the dose-response curve to the right but also prevented the tendency to increase retention latencies of the two higher doses. The two lower doses of beta-endorphin did not lengthen latencies to step-through of mice that had not received a footshock during the training while, under these conditions, the two higher doses of the peptide significantly increased latencies to step-through. This effect was prevented by naloxone (0.1 mg/kg). Taken together these results suggest that the effects of beta-endorphin on retention are the consequence of an interaction with opioid receptors and indicate that the right ascending arm of the dose-response curve would probably be due to a punitive effect of beta-endorphin which was also prevented by naloxone. The impairing effect of post-training administration of beta-endorphin (0.10 microgram/kg) on memory was time-dependent, since it was decreased as the training-treatment interval was increased. These results rule out a pharmacological proactive effect of beta-endorphin on retention performance and suggest that beta-endorphin affects memory consolidation. The simultaneous administration of beta-endorphin (0.10 microgram/kg) with the central muscarinic agonist oxotremorine (12.5 or 50.0 micrograms/kg) completely prevented the impairment of retention induced by beta-endorphin, while the simultaneous administration of the central-acting anticholinesterase physostigmine (17 or 68 micrograms/kg) only partially but significantly attenuated the effect of beta-endorphin on retention. Further, the peripheral-acting anticholinesterase neostigmine (68 micrograms/kg) and the nicotinic blocker hexamethonium (5 mg/kg) modified neither retention nor the behavioral effects of beta-endorphin. These results suggest that the impairment of retention induced by beta-endorphin is probably due to an inhibition of acetylcholine release at central cholinergic synapses which are critical for memory formation.