Induction of depolarization block in midbrain dopamine neurons by repeated administration of haloperidol: analysis using in vivo intracellular recording.
Induction of depolarization block in midbrain dopamine neurons by repeated administration of haloperidol: analysis using in vivo intracellular recording.
复制标题
DOI：
--
复制
发表时间：
1986-09
期刊：
影响因子：
--
通讯作者：
A. Grace;B. Bunney
中科院分区：
文献类型：
--
作者：
A. Grace;B. Bunney
抗精神病药物氟哌啶醇的急性给药导致放电率和黑质中自发活性多巴胺神经元的比例增加。相反，氟哌啶醇重复给药21天导致多巴胺神经元显示自发电生理活动的数量急剧减少。在体内的细胞内记录显示，这些nonfiring多巴胺神经元的膜电位显着更去极化比多巴胺神经元在对照组大鼠，虽然他们的输入电阻是相等的。显示这种去极化阻滞的神经元不能被去极化电流注入激活，但可以响应于膜的超极化而被激发。此外，直接作用的多巴胺受体激动剂阿扑吗啡的自身受体选择性剂量的管理超极化失活的多巴胺神经元在治疗的大鼠，导致自发活动的启动。因此，反复给予精神抑制剂似乎会引起对黑质多巴胺神经元的反馈兴奋性驱动，其幅度足以使膜超出尖峰产生区域。其结果是，诱发自发性锋电位活动的强直性去极化阻滞。
Acute administration of the antipsychotic drug haloperidol causes an increase in the firing rate and in the proportion of spontaneously active dopamine neurons in the substantia nigra. In contrast, repeated administration of haloperidol for 21 days results in a dramatic decrease in the number of dopamine neurons displaying spontaneous electrophysiological activity. In vivo intracellular recordings revealed that these nonfiring dopamine neurons have a membrane potential significantly more depolarized than dopamine neurons in control rats, although their input resistances were equivalent. Neurons displaying this depolarization block could not be activated by depolarizing current injection, but could be made to fire in response to hyperpolarization of the membrane. Furthermore, administration of autoreceptor-selective doses of the direct acting dopamine agonist apomorphine hyperpolarized inactivated dopamine neurons in treated rats, resulting in initiation of spontaneous activity. Thus, repeated administration of neuroleptics appears to cause a feedback excitatory drive to nigral dopamine neurons of sufficient magnitude to depolarize the membrane beyond the spike generating region. As a result, a tonic depolarization blockade of spontaneous spike activity is induced.