Enhancement of the Post-training Cholinergic Tone Antagonizes the Impairment of Retention Induced by a Nitric Oxide Synthase Inhibitor in Mice

Author： Kopf S.R. Baratti C.M.

Publisher： Academic Press

ISSN： 1074-7427

Source： Neurobiology of Learning and Memory, Vol.65, Iss.3, 1996-05, pp. : 207-212

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

The present experiments examined the role of the central cholinergic system in the memory impairment induced by post-training administration of a nitric oxide synthase (NOS) inhibitor in mice. Male Swiss mice received a one-trial inhibitory avoidance training (0.8 mA, 50 Hz, 1-s footshock) followed immediately by an ip injection of the NOS inhibitor l - N G -nitroarginine methyl ester ( l -NAME; 100 mg/kg). Retention (cut-off time, 300 s) was tested 48 h after training. The administration of l -NAME results in memory impairment for the inhibitory avoidance task. The effects of l -NAME (100 mg/kg, ip) on retention were reversed in a dose-related manner by the centrally acting anticholinesterase physostigmine (35, 70, or 150 mug/kg, sc) administered 30 min after the NOS inhibitor. Further, l -NAME (100 mg/kg, ip)-induced memory impairment was completely antagonized by the centrally acting muscarinic cholinergic agonist oxotremorine (OTM; 25, 50, or 100 mug/kg, sc) when given 30 min after l -NAME. The peripherally acting anticholinesterase neostigmine (150 mug/kg, sc) did not modify the memory-impairing effects of l -NAME. These findings suggest that the memory impairment following post-training administration of a NOS inhibitor is mediated, at least in part, by a reduction of the activity of central muscarinic cholinergic mechanisms and are consistent with our previous view that nitric oxide may be involved in post-training neural processes underlying the storage of newly acquired information.