Assessment of the muscarinic receptor subtype involved in the mediation of pilocarpine-induced purposeless chewing behaviour.
Purposeless chewing behaviour in rats was enhanced by intraperitoneal administration of the muscarinic agonists pilocarpine (1.0-8.0 mg/kg), RS 86 (0.5-0.8 mg/kg), oxotremorine (1-2 mg/kg) and arecoline (2-32 mg/kg), but not by nicotine (0.1-3.2 mg/kg). Chewing behaviour was also induced by the ICV administration of the muscarinic agonists carbachol (12.5-100 micrograms) and pilocarpine (50-200 micrograms), but not by the putative M-1 receptor agonist McN-A-343 (50-200 micrograms) or AH 6405 (100-200 micrograms). The muscarinic receptor antagonists scopolamine (0.01-0.1 mg/kg SC), benzhexol (0.075-2.5 mg/kg SC), secoverine (1-10 mg/kg SC), and dicyclomine (1.25-10 mg/kg SC) antagonised purposeless chewing behaviour induced by pilocarpine (4 mg/kg IP). AF-DX 116 (2.5-100 mg/kg SC), an M-2 antagonist, partially inhibited the actions of pilocarpine (4 mg/kg IP). Based on ED40 values the rank order of potency following IP administration was scopolamine greater than benzhexol greater than secoverine greater than dicyclomine greater than AF-DX 116. The ICV administration of the muscarinic antagonists N-methylscopolamine (2.5-10 micrograms) and oxyphenonium (10-40 micrograms) antagonised chewing behaviour induced by pilocarpine (4 mg/kg IP) in a dose-related manner. The M-2 antagonist 4-DAMP (40-160 micrograms ICV), as well as AF-DX 116 (40-160 micrograms ICV), also inhibited the effects of pilocarpine (40-160 micrograms ICV). The putative M-1 receptor antagonist pirenzepine (80-320 micrograms ICV) did not antagonise chewing behaviour induced by pilocarpine (4 mg/kg IP).(ABSTRACT TRUNCATED AT 250 WORDS)
Stewart
B R
BR
University Department of Neurology, Institute of Psychiatry, London, UK.
Jenner
P
P
Marsden
C D
CD
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002404:Catheterization; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D010277:Parasympathomimetics / Q000008:administration & dosage / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013238:Stereotaxic Techniques
D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D010862:Pilocarpine