The Post-training Memory Enhancement Induced by Physostigmine and Oxotremorine in Mice Is Not State-Dependent

Abstract

Immediate post-training subcutaneous administration of either the centrally acting anticholinesterase physostigmine (35, 70, or 150 μg/kg) or the centrally acting muscarinic cholinergic agonist oxotremorine (OTM; 25, 50, or 100 μg/kg) significantly enhanced retention of male Swiss mice tested 48 h after training in a one-trial step-through inhibitory avoidance task (0.8 mA, 50 Hz, 1 s footshock). Neither physostigmine nor OTM affected latencies to step through in mice not given the footshock on the training trial, suggesting that the effects of both cholinomimetics on retention performance were not due to nonspecific actions on response test latencies. The peripherally acting anticholinesterase neostigmine (35, 70, or 150 μg/kg) did not significantly influence retention latencies of either shocked or unshocked mice. The influences of physostigmine (150 μg/kg) and OTM (100 μg/kg) on retention were time-dependent, which suggests that the drugs facilitated memory storage. Administration of physostigmine (150 μg/kg) or OTM (100 μg/kg) 30 min prior to the retention test did not affect the retention performance of mice given post-training injections of either saline, physostigmine (150 μg/kg), or OTM (100 μg/kg). Considered together, these findings indicate that the memory-enhancing effects of post-training administration of physostigmine or OTM are not state-dependent and are consistent with the view that the behavioral effects of the cholinomimetics drugs are mediated through an interaction with the neural processes underlying the storage of acquired information.