Sills M A, Mellow A M, Sunderland T, Jacobowitz D M
Section on Histopharmacology, National Institute of Mental Health, Bethesda, MD 20892.
Brain Res. 1988 Jun 21;453(1-2):385-8. doi: 10.1016/0006-8993(88)90184-9.
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.
已知促甲状腺激素释放激素(TRH)通过中枢作用机制在大鼠中引发湿狗样抖动。在本研究中,研究了毒蕈碱型胆碱能拮抗剂抑制TRH介导的湿狗样抖动的能力。长效TRH类似物MK-771,剂量为1.0、1.5和3.0mg/kg,以剂量依赖性方式引发湿狗样抖动。中枢作用的毒蕈碱型胆碱能拮抗剂阿托品和东莨菪碱,剂量分别为5和0.8mg/kg,仅显著降低最高剂量的MK-771引发湿狗样抖动的能力。当检测外周作用的拮抗剂甲基东莨菪碱和甲基阿托品时,发现它们分别在5和0.8mg/kg剂量下不能显著降低MK-771产生的湿狗样抖动。本研究结果表明,胆碱能拮抗剂以非竞争性方式抑制MK-771诱导的湿狗样抖动,并支持TRH介导的湿狗样抖动受中枢毒蕈碱型胆碱能系统调节的观点。