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 3H-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 (Bmax) in rats that received repeated scopolamine injections as compared to saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Baskin
P P
PP
Department of Psychology, University of Connecticut, Storrs 06269-1020.
Gianutsos
G
G
Salamone
J D
JD
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology*; D011813:Quinuclidinyl Benzilate; D051381:Rats; D017207:Rats, Sprague-Dawley; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012601:Scopolamine / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*
D011976:Receptors, Muscarinic; D010862:Pilocarpine; D011813:Quinuclidinyl Benzilate; D012601:Scopolamine