Subchronic Effects of Phencyclidine on Dopamine and Serotonin Receptors: Implications for Schizophrenia
Subchronic Effects of Phencyclidine on Dopamine and Serotonin Receptors: Implications for Schizophrenia
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DOI：
10.1007/s12031-009-9204-9
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发表时间：
2009-07-01
影响因子：
3.1
通讯作者：
Tarazi, Frank I.
中科院分区：
文献类型：
--
作者：
Choi, Yong Kee;Snigdha, Shikha;Tarazi, Frank I.
亚慢性苯环利定（PCP）治疗（2 mg/kg，持续7天，每日两次，随后7天停药）后，通过放射自显影定量分析了与精神分裂症的病理生理学和治疗有关的代表性多巴胺（D-1、D-2和D-4）和5-羟色胺（5-HT 1A和5-HT 2A）受体的变化。这种治疗在成年大鼠中持续诱导了强大和持久的认知缺陷，尽管导致PCP诱导的认知缺陷的分子机制尚未确定。重复PCP处理显著降低了内侧和外侧尾壳核中D-1受体的标记（分别为22%和23%），并增加了内侧前额叶（26%）和背外侧额叶皮质（30%）中的5 HT（1A）受体结合。在其他脑区未检测到D-1或5 HT（1A）受体的变化。这些结果表明，纹状体D-1受体的下调和皮质5 HT（1A）受体的上调可能有助于PCP诱导的大鼠认知功能障碍。亚慢性五氯苯酚处理并没有改变D-2、D-4和5 HT（2A）受体在所有脑区的水平，这表明这些受体在介导五氯苯酚在成年大鼠中的亚慢性作用中的作用很小。
Changes in representative dopamine (D-1, D-2, and D-4) and serotonin (5-HT1A and 5-HT2A) receptors that have been implicated in the pathophysiology and treatment of schizophrenia were autoradiographically quantified after subchronic phencyclidine (PCP) treatment (2 mg/kg for 7 days, bi-daily followed by 7 days drug free). This treatment has consistently induced robust and long-lasting cognitive deficits in adult rats, although the molecular mechanisms contributing to PCP-induced cognitive deficits remain undefined. Repeated PCP treatment significantly decreased labeling of D-1 receptors in the medial and lateral caudate-putamen (22% and 23%, respectively) and increased 5HT(1A) receptor binding in the medial-prefrontal (26%) and dorsolateral-frontal cortex (30%). No changes in D-1 or 5HT(1A) receptors were detected in other brain regions. These findings suggest that downregulation of striatal D-1 receptors and upregulation of cortical 5HT(1A) receptors may contribute to PCP-induced impairment of cognitive functions in rats. Subchronic PCP treatment did not alter levels of D-2, D-4, and 5HT(2A) receptors in all brain regions examined, which suggests a minimal role for these receptors in mediating subchronic actions of PCP in adult rats.