Stone Eric A, Lin Yan, Ahsan Mohammad R, Quartermain David
Department of Psychiatry, New York University School of Medicine, 550 First Ave., New York, NY, 10016, USA.
Psychopharmacology (Berl). 2005 Nov;183(1):127-32. doi: 10.1007/s00213-005-0171-8. Epub 2005 Oct 22.
Central alpha(1)- and alpha(2)-adrenoceptors in a number of different brain regions are known to have opposing actions on gross behavioral activity, with the former stimulating and the latter inhibiting activity. Therefore, blockade of alpha(1)-receptors may induce inactivity by leading to unopposed alpha(2) activity.
The aim of this study was to test if central blockade of alpha(2)-receptor function restores behavioral activity in alpha(1)-receptor-blocked mice.
Dose-response studies were undertaken on the effects of alpha(1)- and alpha(2)-agonists and antagonists microinjected into the dorsal pons on gross behavioral activity in a novel cage test.
The behavioral inactivity resulting from blockade of alpha(1)-receptors in the pons with the antagonist, terazosin, was reversed by either a low dose of an alpha(2)-antagonist, atipamezole, or a low dose of an alpha(2)-agonist, dexmedetomidine, but was exacerbated by a high dose of the alpha(2)-agonist.
The results support the hypothesis that blockade of alpha(1)-receptors in the dorsal pons of mice produces inactivity by causing unopposed activity of alpha(2)-receptors. This condition may be relevant to inactive states seen after stress or during depressive illness.
已知在许多不同脑区的中枢α1和α2肾上腺素能受体对总体行为活动具有相反作用,前者刺激活动,后者抑制活动。因此,α1受体阻断可能通过导致α2活性无对抗而诱导活动减少。
本研究的目的是测试中枢α2受体功能阻断是否能恢复α1受体阻断小鼠的行为活动。
在新笼试验中,对微量注射到背侧脑桥的α1和α2激动剂及拮抗剂对总体行为活动的影响进行剂量反应研究。
用拮抗剂特拉唑嗪阻断脑桥中的α1受体所导致的行为活动减少,可被低剂量的α2拮抗剂阿替美唑或低剂量的α2激动剂右美托咪定逆转,但高剂量的α2激动剂会使其加剧。
结果支持以下假设,即小鼠背侧脑桥中α1受体的阻断通过引起α2受体的无对抗活性而导致活动减少。这种情况可能与应激后或抑郁疾病期间出现的不活动状态有关。