Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine
Corticolimbic dopamine neurotransmission is temporally dissociated from the cognitive and locomotor effects of phencyclidine
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DOI：
10.1523/jneurosci.18-14-05545.1998
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发表时间：
1998-07-15
影响因子：
5.3
通讯作者：
Moghaddam, B
中科院分区：
文献类型：
--
作者：
Adams, B;Moghaddam, B
苯环己哌啶（PCP）及其类似物氯胺酮产生的行为综合征代表了精神分裂症某些方面的药理学模型。尽管这些药物具有多方面的特性，但迄今为止，人们一直认为其拟精神病和认知损害作用的主要机制涉及皮质边缘多巴胺系统。本研究检查了皮质边缘多巴胺和谷氨酸神经传递的改变与PCP在啮齿动物中的两种多巴胺依赖性行为效应之间的时间关系，这两种效应与临床现象学相关，即工作记忆受损，其用于模拟与精神分裂症相关的额叶缺陷，以及过度运动，其被用作药物诱发或加重精神病倾向的预测因子。PCP增加多巴胺和谷氨酸流出的前额叶皮层和脑桥核，通过微透析测量。在注射后2.5小时，两个区域中多巴胺的增加保持在高于基线的水平，此时实验终止。然而，自发活动在2009年恢复到基线水平。
The behavioral syndrome produced by phencyclidine (PCP) and its analog ketamine represents a pharmacological model for some aspects of schizophrenia. Despite the multifaceted properties of these drugs, the main mechanism for their psychotomimetic and cognitive-impairing effects has been thought heretofore to involve the corticolimbic dopamine system. The present study examined the temporal relationship between alterations in corticolimbic dopamine and glutamate neurotransmission and two dopamine-dependent behavioral effects of PCP in the rodent that have relevance to the clinical phenomenology, namely, impairment of working memory, which is used to model the frontal lobe deficits associated with schizophrenia, and hyperlocomotion, which is used as a predictor of the propensity of a drug to elicit or exacerbate psychosis. PCP increased dopamine and glutamate efflux in the prefrontal cortex and nucleus accumbens, as measured by microdialysis. The increase in dopamine in both regions remained elevated well above baseline 2.5 hr after the injection, at which time the experiment was terminated. However, locomotor activity returned to baseline in