ENHANCEMENT OF THE POST-TRAINING CHOLINERGIC TONE ANTAGONIZES THE IMPAIRMENT OF RETENTION INDUCED BY A NITRIC-OXIDE SYNTHASE INHIBITOR IN MICE

The present experiments examined the role of the central cholinergic s ystem in the memory impairment induced by post-training administration of a nitric oxide synthase (NOS) inhibitor in mice. Male Swiss mice r eceived a one-trial. inhibitory avoidance training (0.8 mA, 50 Hz, 1-s footshock) followed immediately by an ip injection of the NOS inhibit or L-N-G-nitroarginine methyl ester (L-NAME; 100 mg/kg). Retention (cu t-off time, 300 s) was tested 48 h after training. The administration of L-NAME results in memory impairment for the inhibitory avoidance ta sk. The effects of L-NAME (100 mg/kg, ip) on retention were reversed i n a dose-related manner by the centrally acting anticholinesterase phy sostigmine (35, 70, or 150 mu g/kg, sc) administered 30 min after the NOS inhibitor. Further, L-NAME (100 mg/kg, ip)-induced memory impairme nt was completely antagonized by the centrally acting muscarinic choli nergic agonist oxotremorine (OTM; 25, 50, or 100 mu g/kg, sc) when giv en 30 min after L-NAME. The peripherally acting anticholinesterase neo stigmine (150 mu g/kg, sc) did not modify the memory-impairing effects of L-NAME. These findings suggest that the memory impairment followin g post-training administration of a NOS inhibitor is mediated, at leas t in part, by a reduction of the activity of central muscarinic cholin ergic mechanisms and are consistent with our previous view that nitric oxide may be involved in post-training neural processes underlying th e storage of newly acquired information. (C) 1996 Academic Press, Inc.