Heidenreich Byron A, Mitrovic Igor, Battaglia George, Napier T Celeste
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
Exp Neurol. 2004 Apr;186(2):145-57. doi: 10.1016/j.expneurol.2003.11.004.
Neurons in the ventral pallidum (VP) exhibit robust responding to activation of dopamine (DA) receptors of the D1 class. To determine if the VP adapts to chronic cessation of DA transmission, the present studies examined D1 receptor-mediated responses in the VP recorded extracellularly in chloral-hydrate anesthetized rats following destruction of DA neurons with 6-hydroxydopamine (6-OHDA) or long-term treatment with the D1 antagonist SCH23390. Indices of basal spiking (i.e., spontaneous firing rate and pattern) recorded 10-21 days after unilateral 6-OHDA treatment did not differ from controls. Moreover, DA depletion did not alter the proportion of VP neurons whose rate was enhanced with i.v. injections of the D1 agonist SKF38393, and the functional efficacy (Emax) and potency (ED50) were similar to controls. There also was no change in the direction of responses, the Emax or the ED50 measure of sensitivity (ECur50) to iontophoretic application of DA or SKF38393 in VP neurons. Forty-eight hours after 21 once-daily treatments with SCH23390, the number of [3H]SCH23390-labeled D1 receptors was increased in the striatum, but unchanged in the VP, globus pallidus, or septum. Accordingly, there was no functional upregulation of VP responses to i.v. SKF38393. Indeed, the proportion of SKF38393-sensitive neurons was decreased after chronic SCH23390. Distinguishing the VP from other forebrain regions, these findings indicate that basal spiking is not altered in the VP following chronic DA depletion, and that no upregulation of VP DA receptor function occurs following either dopaminergic lesions or chronic antagonism of D1 receptors.
腹侧苍白球（VP）中的神经元对D1类多巴胺（DA）受体的激活表现出强烈反应。为了确定VP是否适应DA传递的长期停止，本研究检测了在用6-羟基多巴胺（6-OHDA）破坏DA神经元或用D1拮抗剂SCH23390长期治疗后，水合氯醛麻醉大鼠的VP中细胞外记录的D1受体介导的反应。单侧6-OHDA治疗10 - 21天后记录的基础放电指标（即自发放电率和模式）与对照组无差异。此外，DA耗竭并未改变静脉注射D1激动剂SKF38393后放电率增加的VP神经元比例，其功能效能（Emax）和效价（ED50）与对照组相似。VP神经元对DA或SKF38393离子电渗应用的反应方向、Emax或敏感性测量指标（ECur50）也没有变化。在用SCH23390每日一次治疗21次后的48小时，纹状体中[3H]SCH23390标记的D1受体数量增加，但VP、苍白球或隔区中的数量未变。因此，VP对静脉注射SKF38393的反应没有功能上调。实际上，慢性SCH23390治疗后，SKF38393敏感神经元的比例降低。这些结果表明，与其他前脑区域不同，慢性DA耗竭后VP的基础放电没有改变，并且在多巴胺能损伤或D1受体慢性拮抗后，VP的DA受体功能没有上调。
