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Pharmacological evidence of a central effect of naltrexone, morphine, and β-endorphin and a peripheral effect of met- and leu-enkephalin on retention of an inhibitory response in mice

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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 β-endorphin (0.1 μg/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 met-enkephalin (1.0 μg/kg) and leu-enkephalin (0.3 μg/kg) on retention. Those results suggest that enkephalins affect retention through influences initiated peripherally. Thus, different sites and mechanisms of action for β-endorphin and the enkephalins are proposed.

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    We thank Professor H. Merz, Boehringer Ingelheim Labs, for his generous gift of MR 2263. Preparation of this paper, in part, was supported by USPHS Research Grants MH 12526 and AG 00538 and Contract N00014-84-K-0391 from the Office of Naval Research (to J.L.McG.). Address of Dr. Baratti: Catedra de Farmacologia de la Facultad de farmacia y Bioquimica de la Universidad de Buenos Aires, Junin 956 5* piso RA 1113, Buenos Aires, Argentina.

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