Central muscarinic cholinergic antagonists block wet-dog shakes produced by the TRH analog MK-771 in the rat.
Thyrotropin-releasing hormone (TRH) is known to elicit wet-dog shakes in rats through a central mechanism of action. In the present study, the ability of muscarinic cholinergic antagonists to inhibit TRH-mediated wet-dog shakes was examined. The longer-acting TRH analog, MK-771, at doses of 1.0, 1.5 and 3.0 mg/kg elicited wet-dog shakes in a dose-dependent manner. The centrally-acting muscarinic cholinergic antagonists, atropine and scopolamine, at doses of 5 and 0.8 mg/kg, respectively, significantly reduced the ability of only the highest dose of MK-771 to elicit wet-dog shakes. When the peripherally-acting antagonists, methylscopolamine and methylatropine, were examined, they were not found to significantly reduce wet-dog shakes produced by MK-771 at doses of 5 and 0.8 mg/kg, respectively. The results of this study suggest that cholinergic antagonists inhibit MK-771-induced wet-dog shakes in a noncompetitive manner and support the view that TRH-mediated wet-dog shakes are modulated by central muscarinic cholinergic systems.
D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D009069:Movement Disorders / Q000139:chemically induced* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology*; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*
D011976:Receptors, Muscarinic; D053778:Thiazolidines; D013973:Thyrotropin-Releasing Hormone; C021597:pyro(l-alpha-aminoadipyl)-L-histidyl-L-thiazolidine-4-carboxamide; D001285:Atropine; D012601:Scopolamine