Effects of acute and chronic administration of phencyclidine on the A10 dopaminergic mesolimbic system: electrophysiological and behavioral correlates.
Effects of acute and chronic administration of phencyclidine on the A10 dopaminergic mesolimbic system: electrophysiological and behavioral correlates.
复制标题
苯环己哌啶急性和慢性给药对 A10 多巴胺能中脑边缘系统的影响：电生理学和行为相关性。
DOI：
10.1016/0028-3908(88)90093-7
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发表时间：
1988
影响因子：
4.7
通讯作者：
French,ED
中科院分区：
文献类型：
--
作者：
French,ED
采用电生理学和行为学方法评估长期暴露于苯环己哌啶（PCP，5 mg/kg/天，持续 30 天）对大鼠腹侧被盖 A10 多巴胺能神经元以及运动和共济失调行为的影响。腹侧被盖单个神经元的细胞外记录显示，长期用盐水或五氯苯酚治疗的大鼠之间只有微小的差异。累积剂量反应曲线上升部分的比较表明，长期使用该药物治疗的动物只需要比对照组多 0.4 倍的 PCP 即可产生同等的神经元放电率变化。此外，由 PCP 诱导的 A10 神经元活性的平均最大增加在药物治疗的大鼠中为 43%，而对照组为 60%。尽管这些是适度的量变，但 A10 神经元对 PCP 的反应存在显着的质的差异。虽然 PCP 对对照组的放电率产生了特征性的剂量依赖性双相效应，但长期用 PCP 治疗的动物中不存在反应的下降（抑制）成分。与最小的电生理学变化同时，总体运动活动的测量表明，对第三十次（30次）注射五氯苯酚的反应实际上与第一次接触相同动物后测量的反应相同。然而，相反，伴随多动症的共济失调在治疗过程中迅速减弱。因此，长期接触 PCP 似乎并没有显着降低 PCP 激活 A10 神经元（包括中皮质边缘多巴胺能系统）的能力。事实上，长期长期使用五氯苯酚，较大剂量实际上可能会导致中脑多巴胺能神经元受到更大程度的刺激。这种效应可能部分是长期滥用五氯苯酚最终导致类似精神病的人格改变的神经生物学机制的基础。
Electrophysiological and behavioral methods were used to evaluate the effects of chronic exposure to phencyclidine (PCP, 5 mg/kg/day for 30 days) on ventral tegmental A10dopaminergic neurons and locomotor and ataxic behavior in the rat. Extracellular recordings from single neurons in the ventral tegmentum showed only minimal differences between rats chronically treated with either saline or PCP. A comparison of the rising portion of the cumulative dose-response curves indicated that the animals treated chronically with the drug required only 0.4 times more PCP than the controls to produce equivalent changes in neuronal firing rates. Also, the average maximum increase in activity in A10neurons, induced by PCP, was 43% in the drug-treated rats compared to 60% in the controls. Although these were moderate quantitative changes, a marked qualitative difference in the response of A10neurons to PCP was seen. Whereas PCP elicited a characteristic dose-dependent biphasic effect on the firing rates in the control group, the declining (inhibitory) component of the response was not present in the animals chronically treated with PCP. In parallel with the minimal electfophysiological changes, measurements of gross locomotor activity showed that the response to the thirtieth (30th) injection of PCP was virtually identical to that measured in the same animals following the first exposure. In contrast, however, the ataxia which accompanied the hyperactivity rapidly diminished over the course of treatment. It would appear, therefore, that chronic exposure to PCP did not substantially diminish the ability of PCP to activate the A10neurons, comprising the mesocorticolimbic dopaminergic systems. In fact, with long-term chronic use of PCP, larger doses may actually result in a greater degree of stimulation of midbrain dopaminergic neurons. This effect may partially underly the neurobiological mechanism by which chronic abuse of PCP can eventually lead to psychotic-like personality changes.