Selective antagonists provide evidence that M1 muscarinic receptors may mediate carbachol-induced drinking in the rat.
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.
Polidori
C
C
Institute of Pharmacology, University of Camerino, Italy.
Massi
M
M
Lambrecht
G
G
Mutschler
E
E
Tacke
R
R
Melchiorre
C
C
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*
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D000804:Angiotensin II; D010890:Pirenzepine; D002217:Carbachol