Effects of central nicotinic cholinergic receptor blockade produced by chlorisondamine on learning and memory performance in rats.
The effects of chronic nicotinic receptor blockade on the performance of learning and memory tasks were determined using chlorisondamine, a compound which produces central nicotinic cholinergic receptor blockade that lasts for several weeks after a single icv administration. Chlorisondamine treatment did not affect the acquisition of spatial information in the Morris water maze or in the radial arm maze, tasks in which performance is reportedly disrupted by acute administration of the nicotinic antagonist, mecamylamine. Chlorisondamine also did not affect performance in the inhibitory avoidance task and did not alter the memory enhancement found in this task after post-training administration of nicotine. Mecamylamine, however, completely blocked the memory-enhancing effects of nicotine. In contrast to the differential ability to chlorisondamine and mecamylamine to block nicotine's memory-enhancing effects, these antagonists produced comparable blockade of nicotine's effects on open field behavior. It is unlikely that the different effects of systemically administered mecamylamine and centrally administered chlorisondamine on nicotine-induced memory enhancement are due to mecamylamine's peripheral effects, since hexamethonium, a peripherally active nicotinic antagonist, did not block nicotine-induced memory enhancement. The different pattern of effects of mecamylamine and chlorisondamine may be related to compensatory mechanisms being selectively induced by chronic blockade produced by chlorisondamine and not by acute blockade produced by mecamylamine. Alternatively, different effects of these two nicotinic cholinergic antagonists on the performance of learning and memory tasks might be related to selective actions of these compounds at nicotinic receptor subtypes or at nonnicotinic receptors.
Decker
M W
MW
Neuroscience Research-47W, Pharmaceutical Products Division, Abbott Laboratories, Abbott Park, Illinois 60064.
Majchrzak
M J
MJ
D000818:Animals; D001143:Arousal / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D011939:Mental Recall / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D009949:Orientation / Q000187:drug effects*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012153:Retention, Psychology / Q000187:drug effects; D012931:Social Environment
D011950:Receptors, Cholinergic; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine