Neural basis of the potentiated inhibition of repeated haloperidol and clozapine treatment on the phencyclidine-induced hyperlocomotion.
Neural basis of the potentiated inhibition of repeated haloperidol and clozapine treatment on the phencyclidine-induced hyperlocomotion.
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DOI：
10.1016/j.pnpbp.2012.03.007
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发表时间：
2012-08-07
影响因子：
5.6
通讯作者：
Li, Ming
中科院分区：
文献类型：
--
作者：
Zhao, Changjiu;Sun, Tao;Li, Ming
临床观察表明，抗精神病药物的作用很早就开始，并随着时间的推移逐渐增强。在大鼠苯环利定（PCP）诱导的过度运动模型中可以捕捉到这一时间过程的抗精神病作用，因为反复的抗精神病药物治疗逐渐增加了对反复PCP诱导的过度运动的抑制作用。虽然急性抗精神病药物作用的神经基础已被广泛研究，但介导反复抗精神病药物治疗增强效应的系统尚未阐明。在本研究中，我们研究了氟哌啶醇（HAL）和氯氮平（CLZ）治疗在反复pcp诱导的过度运动中的增强作用的神经解剖学基础。每天1次，连续5天，先给成年雄性sd大鼠注射HAL （0.05 mg/kg, sc）、CLZ （10.0 mg/kg, sc）或生理盐水，30分钟后再注射PCP （3.2 mg/kg, sc）或生理盐水，注射PCP后90分钟测量运动活动。在急性（第1天）或重复（第5天）药物试验后评估C-Fos免疫反应性。行为上，在5天的药物测试中，反复使用HAL或CLZ治疗逐渐增加了对pcp诱导的过度运动的抑制。神经解剖学上，急性和反复治疗HAL均显著增加了pcp诱导的伏隔核壳（NAs）和腹侧被盖区（VTA）的c-Fos表达，但降低了中央杏仁核（CeA）的c-Fos表达。急性和反复CLZ治疗显著增加pcp诱导的中隔外侧核（LSv）腹侧部和VTA的c-Fos表达，但降低内侧前额叶皮层（mPFC）的c-Fos表达。更重要的是，从第1天到第5天，HAL和CLZ在这些大脑区域的作用经历了时间依赖性的减少。这些发现表明，重复HAL通过作用于NAs、CeA和VTA来实现对pcp诱导的过度运动的增强抑制，而CLZ通过作用于mPFC、LSv和VTA来实现。
Clinical observations suggest that antipsychotic effect starts early and increases progressively over time. This time course of antipsychotic effect can be captured in a rat phencyclidine (PCP)-induced hyperlocomotion model, as repeated antipsychotic treatment progressively increases its inhibition of the repeated PCP-induced hyperlocomotion. Although the neural basis of acute antipsychotic action has been studied extensively, the system that mediates the potentiated effect of repeated antipsychotic treatment has not been elucidated. In the present study, we investigated the neuroanatomical basis of the potentiated action of haloperidol (HAL) and clozapine (CLZ) treatment in the repeated PCP-induced hyperlocomotion. Once daily for five consecutive days, adult Sprague-Dawley male rats were first injected with HAL (0.05 mg/kg, sc), CLZ (10.0 mg/kg, sc) or saline, followed by an injection of PCP (3.2 mg/kg, sc) or saline 30 min later, and motor activity was measured for 90 min after the PCP injection. C-Fos immunoreactivity was assessed either after the acute (day 1) or repeated (day 5) drug tests. Behaviorally, repeated HAL or CLZ treatment progressively increased the inhibition of PCP-induced hyperlocomotion throughout the five days of drug testing. Neuroanatomically, both acute and repeated treatment of HAL significantly increased PCP-induced c-Fos expression in the nucleus accumbens shell (NAs) and the ventral tegmental area (VTA), but reduced it in the central amygdaloid nucleus (CeA). Acute and repeated CLZ treatment significantly increased PCP-induced c-Fos expression in the ventral part of lateral septal nucleus (LSv) and VTA, but reduced it in the medial prefrontal cortex (mPFC). More importantly, the effects of HAL and CLZ in these brain areas underwent a time-dependent reduction from day 1 to day 5. These findings suggest that repeated HAL achieves its potentiated inhibition of the PCP-induced hyperlocomotion by acting on the NAs, CeA and VTA, while CLZ does so by acting on the mPFC, LSv and VTA.
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影响因子：
17.7
作者：
Kapur, S;Arenovich, T;Jones, B
通讯作者：
Jones, B
影响因子：
3.6
作者：
Doat-Meyerhoefer, MM;Hard, R;Rabin, RA
通讯作者：
Rabin, RA
DOI：
10.1073/pnas.89.13.5764
发表时间：
1992-07-01
影响因子：
11.1
作者：
HOPE, B;KOSOFSKY, B;NESTLER, EJ
通讯作者：
NESTLER, EJ
影响因子：
3.3
作者：
CARBONI, E;IMPERATO, A;DICHIARA, G
通讯作者：
DICHIARA, G
影响因子：
10.6
作者：
Leucht, S;Busch, R;Kane, JM
通讯作者：
Kane, JM