Antagonism of diazepam's anticonflict effects in rats by nicotine, but not by arecoline

Abstract

AbstractThe purpose of the present study was to determine the possible role of cholinergic mechanisms in the anticonflict effects of the anxiolytic diazepam. Male Sprague‐Dawley rats were tested with a modified Geller‐Seifter procedure using a multiple reinforcement schedule in which unpunished responding in one component was reinforced according to a fixed‐interval 60‐sec schedule, and punished responding in the other component resulted in both food and a brief electric shock presentation according to a fixed‐ratio 1 schedule. In Experiment 1 (−)‐nicotine antagonized the increase in punished responding that was produced by diazepam. In Experiment 2 diazepam produced selective increases in punished responding that again was antagonized by (−)‐nicotine, a nicotinic cholinergic agonist, whereas arecoline, a muscarinic cholinergic agonist, did not antagonize diazepam's increase in punished responding. Neither drug produced any significant changes in unpunished responding. In Experiment 3 it was shown that the centrally acting nicotinic antagonist, mecamylamine, was able to block nicotine's antagonism of diazepam. These results suggest that there is an interaction between central nicotinic cholinergic mechanisms and diazepam's anticonflict effects in this animal model for anxiolytics, and support clinical observations that smoking can reduce some effects of benzodiazepines. © 1994 Wiley‐Liss, Inc.