REPEATED SCOPOLAMINE INJECTIONS SENSITIZE RATS TO PILOCARPINE-INDUCED VACUOUS JAW MOVEMENTS AND ENHANCE STRIATAL MUSCARINIC RECEPTOR-BINDING

This experiment was conducted to determine if repeated administration of the muscarinic antagonist scopolamine could increase pilocarpine-induced vacuous jaw movements and also enhance muscarinic receptor binding. Rats received daily injections of either scopolamine (0.5 mg/kg IP) or saline for 14 days. On day 15 rats received no injections of scopolamine, but did receive injections of pilocarpine (1.0, 2.0 or 4.0 mg/kg IP) or saline. After administration of pilocarpine or saline, all. rats were observed for vacuous jaw movements and rearing behavior. The day after pilocarpine injections, rats were sacrificed and samples of tissue from the lateral neostriatum were removed to assess muscarinic receptor binding using H-3-QNB as the ligand. Analyses of the vacuous jaw movement data indicated that there was a significant dose-related increase in vacuous jaw movements induced by pilocarpine, and also that there was a significant enhancement of pilocarpine-induced vacuous jaw movements in rats pretreated with repeated scopolamine injections. There was not a significant scopolamine x pilocarpine interaction, suggesting that pretreatment with scopolamine produced an apparent parallel shift in the pilocarpine dose-response curve. Pilocarpine significantly suppressed rearing behavior, and scopolamine pretreatment significantly enhanced the suppression of rearing produced by pilocarpine. Analysis of the receptor binding data indicated that there was a significant increase in the number of muscarinic receptor sites (B-max) in rats that received repeated scopolamine injections as compared to saline-treated rats. These results demonstrate that repeated administration of scopolamine sensitizes rats to the induction of vacuous jaw movements produced by pilocarpine, and also indicate that vacuous jaw movements may be a useful behavioral procedure for assessing striatal muscarinic supersensitivity.