O'Donnell J M
J Pharmacol Exp Ther. 1987 Aug;242(2):588-94.
The results of a number of studies have implicated beta adrenergic receptors in the brain in the actions of proven antidepressant drugs. This suspected involvement of central beta adrenergic receptors made it of interest to characterize the behavioral effects of centrally acting beta adrenergic agonists. Clenbuterol and prenalterol, unlike most beta adrenergic agonists, penetrate into the central nervous system after peripheral administration. In the present study, the effects of these agonists on behavior maintained under a multiple fixed-interval 5-min, fixed-ratio 30-response schedule were determined. Both compounds, in a dose-dependent manner, reduced response rate under both components of the multiple schedule. Under the fixed-interval component, clenbuterol and prenalterol altered the temporal pattern of responding. At no dose tested was there evidence for any stimulant action of either of the drugs. The effects of clenbuterol and prenalterol on behavior maintained under the multiple schedule appeared to be a result of an interaction of the agonists with beta adrenergic receptors. This was evidenced by the ability of the beta adrenergic antagonist propranolol to block the effects of the agonists. The behavioral effects of clenbuterol and prenalterol appear, in general, to be similar to effects reported previously for tricyclic and monoamine oxidase inhibiting antidepressant drugs.
多项研究结果表明,已证实的抗抑郁药物的作用与大脑中的β-肾上腺素能受体有关。中枢β-肾上腺素能受体的这种疑似参与使得研究中枢作用的β-肾上腺素能激动剂的行为效应变得很有意义。与大多数β-肾上腺素能激动剂不同,克仑特罗和普瑞特罗在外周给药后可穿透进入中枢神经系统。在本研究中,测定了这些激动剂对在多重固定间隔5分钟、固定比率30次反应时间表下维持的行为的影响。两种化合物均以剂量依赖的方式降低了多重时间表两个组成部分下的反应率。在固定间隔组成部分下,克仑特罗和普瑞特罗改变了反应的时间模式。在所测试的任何剂量下,均未发现这两种药物有任何兴奋作用的证据。克仑特罗和普瑞特罗对在多重时间表下维持的行为的影响似乎是激动剂与β-肾上腺素能受体相互作用的结果。β-肾上腺素能拮抗剂普萘洛尔能够阻断激动剂的作用,这证明了这一点。总体而言,克仑特罗和普瑞特罗的行为效应似乎与先前报道的三环类和单胺氧化酶抑制性抗抑郁药物的效应相似。