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D-苯丙胺和氟哌啶醇对中脑边缘多巴胺能神经元终末兴奋性的调节作用。

Modulation of terminal excitability of mesolimbic dopaminergic neurons by D-amphetamine and haloperidol.

作者信息

Mereu G, Westfall T C, Wang R Y

出版信息

Brain Res. 1985 Dec 16;359(1-2):88-96. doi: 10.1016/0006-8993(85)91415-5.

DOI:10.1016/0006-8993(85)91415-5
PMID:3000526
Abstract

Electrophysiological techniques were used to study the changes in the terminal excitability of mesolimbic DA and non-DA neurons following the infusion of D-amphetamine (D-AMP) and haloperidol (HAL) into the nucleus accumbens (NAc) of rats. The amount of current needed to evoke antidromic spikes by electrical stimulation of the NAc was used as an index of the excitability of axon terminals of these neurons. The excitability of DA neurons was decreased by D-AMP and increased by HAL. In addition, the effect produced by D-AMP was reversed by HAL. By contrast, these drugs either induced an opposite effect or were ineffective in inducing changes on the excitability of nerve terminals of mesolimbic non-DA neurons. Infusion of the vehicle or saline produced no effect. D-AMP and HAL were still effective in modulating the excitability of mesolimbic DA nerve terminals after the destruction of NAc neurons by ibotenic acid. The results suggest that the effects seen after D-AMP and HAL are mediated primarily by DA autoreceptors. It is likely that the increase in the current needed for evoking antidromic spikes after infusion of D-AMP into the terminal region is the consequence of DA autoreceptor-mediated hyperpolarization of terminal membranes. On the other hand, HAL could exert its actions by blocking autoreceptor-mediated hyperpolarization.

摘要

采用电生理技术研究了向大鼠伏隔核(NAc)注射D-苯丙胺(D-AMP)和氟哌啶醇(HAL)后中脑边缘多巴胺(DA)能和非DA能神经元终末兴奋性的变化。通过电刺激NAc诱发逆向动作电位所需的电流量被用作这些神经元轴突终末兴奋性的指标。D-AMP可降低DA能神经元的兴奋性,而HAL可增加其兴奋性。此外,HAL可逆转D-AMP产生的效应。相比之下,这些药物对中脑边缘非DA能神经元神经终末的兴奋性要么产生相反的作用,要么无作用。注射溶媒或生理盐水则无效应。在用鹅膏蕈氨酸破坏NAc神经元后,D-AMP和HAL仍能有效调节中脑边缘DA能神经终末的兴奋性。结果表明,D-AMP和HAL产生的效应主要由DA自身受体介导。向终末区域注射D-AMP后诱发逆向动作电位所需电流增加,可能是DA自身受体介导的终末膜超极化的结果。另一方面,HAL可能通过阻断自身受体介导的超极化发挥作用。

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