title: Selective antagonists provide evidence that M1 muscarinic receptors may mediate carbachol-induced drinking in the rat.
abstract: The present study served to investigate the ability of seven selective muscarinic antagonists to inhibit carbachol-induced drinking in the rat. The muscarinic antagonists were given by intracerebroventricular (i.c.v.) injection 1 min before the i.c.v. injection of carbachol (1 microgram/rat). The M2 antagonist, methoctramine, was inactive up to 80.3 nmol/rat. The M3 antagonist, p-fluoro-hexahydro-sila-difenidol, elicited a modest (42%) but statistically significant inhibition of drinking only at 80 nmol/rat. On the other hand, the selective M1 antagonists, (R)-trihexphenidyl, o-methoxy-sila-hexocyclium and pirenzepine, produced a marked and dose-dependent inhibition of carbachol-induced drinking, their ID50 values being 0.51, 7.36 and 9.31 nmol/rat. Also the M1/M3 antagonists, 4-diphenylacetoxy-N-methylpiperidine methiodide and hexahydro-sila-difenidol, were potent inhibitors of carbachol-induced drinking, their ID50 values (0.28 and 11.09 nmol/rat) being related to their pA2 values for M1 receptors in rabbit vas deferens. These data suggest that carbachol-induced drinking may be mediated by activation of muscarinic M1 receptors.
authors.affiliation: Institute of Pharmacology, University of Camerino, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Polidori
authors.forename: M
authors.initials: M
authors.lastname: Massi
authors.forename: G
authors.initials: G
authors.lastname: Lambrecht
authors.forename: E
authors.initials: E
authors.lastname: Mutschler
authors.forename: R
authors.initials: R
authors.lastname: Tacke
authors.forename: C
authors.initials: C
authors.lastname: Melchiorre
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D018727:Muscarinic Antagonists; D010890:Pirenzepine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
chemical_list: D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000804:Angiotensin II; D010890:Pirenzepine; D002217:Carbachol