O'Donnell J M, Seiden L S
J Pharmacol Exp Ther. 1984 Jun;229(3):629-35.
Performance maintained by differential-reinforcement-of-low-rate operant schedules has been found to be sensitive to antidepressant drugs. Tricyclic antidepressants, monoamine oxidase inhibitors and atypical antidepressants reduce response rate and increase reinforcement rate under long differential-reinforcement-of-low-rate schedules. In order to study the neurochemical mechanism by which the tricyclic antidepressant desipramine alters differential-reinforcement-of-low-rate performance, the effect of desipramine was determined before and after brain catecholamine depletion was induced by 6-hydroxydopamine administration. Before lesioning, desipramine reduced response rate and increased reinforcement rate in a dose-dependent manner. Brain norepinephrine depletion (produced by 6-hydroxydopamine injection into the dorsal noradrenergic bundle) attenuated the ability of desipramine to reduce response rate, but did not alter its ability to increase reinforcement rate, but did not alter its ability to increase reinforcement rate. Brain dopamine depletion, (produced by i.c.v. 6-hydroxydopamine administration after pargyline and desipramine pretreatment) attenuated the ability of desipramine to increase reinforcement rate. These results suggest that the sedative effect of desipramine could be mediated by its interaction with central norepinephrine neurons and that the reinforcement rate-increasing effect may involve central dopamine neurons.
已发现，低速率操作程序的差别强化所维持的行为表现对抗抑郁药物敏感。在长时低速率差别强化程序下，三环类抗抑郁药、单胺氧化酶抑制剂和非典型抗抑郁药会降低反应率并提高强化率。为了研究三环类抗抑郁药地昔帕明改变低速率差别强化表现的神经化学机制，在通过给予6-羟基多巴胺诱导脑儿茶酚胺耗竭之前和之后，测定了地昔帕明的作用。在损伤前，地昔帕明以剂量依赖的方式降低反应率并提高强化率。脑去甲肾上腺素耗竭（通过向背侧去甲肾上腺素能束注射6-羟基多巴胺产生）减弱了地昔帕明降低反应率的能力，但未改变其提高强化率的能力。脑多巴胺耗竭（在帕吉林和地昔帕明预处理后通过脑室内给予6-羟基多巴胺产生）减弱了地昔帕明提高强化率的能力。这些结果表明，地昔帕明的镇静作用可能通过其与中枢去甲肾上腺素神经元的相互作用介导，而强化率增加作用可能涉及中枢多巴胺神经元。
