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 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-NG-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 microg/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 microg/kg, sc) when given 30 min after L-NAME. The peripherally acting anticholinesterase neostigmine (150 microg/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.
Kopf
S R
SR
Laboratorio de Neurofarmacología de Procesos de Memoria, Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, Buenos Aires, RA-1113, Argentina.
Baratti
C M
CM
D000818:Animals; D002799:Cholinergic Fibers / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008568:Memory / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D009388:Neostigmine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000187:drug effects; D010095:Oxotremorine / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology*; D012153:Retention, Psychology / Q000187:drug effects*
D009388:Neostigmine; D010095:Oxotremorine; D010830:Physostigmine; D019001:Nitric Oxide Synthase