Huang Xu-Feng, Tan Yean Yeow, Huang Xin, Wang Qing
Neuroscience Institute of Schizophrenia and Allied Disorders (NISAD), Sydney NSW 2010, Australia.
Neurosci Res. 2007 Nov;59(3):314-21. doi: 10.1016/j.neures.2007.08.001. Epub 2007 Aug 7.
This study examined regional changes of 5-HT(2A and 2C) receptor mRNA expression in the rat brain after chronic administration of clozapine (1.5 mg/kg/day) and haloperidol (2.0 mg/kg/day) for 36 days. 5-HT(2A and 2C) receptor mRNA expression and distributions were detected by in situ hybridization after rats were sacrificed either 2 or 48 h after the last drug administration to examine both immediate and delayed effects following drug withdrawal. Following 2 h of drug withdrawal, it showed that clozapine administration significantly decreased 5-HT(2A) receptor mRNA, predominantly in the nucleus accumbens (65%), hippocampus (80%), lasteral septal nucleus (61%) and striatum (68%) compared to controls, whilst rebound increases were observed in most of these regions 48 h later. In contrast, no change in 5-HT(2A) receptor mRNA expression was found in the haloperidol treated groups either 2 h or 48 h after drug withdrawal. Clozapine also decreased 5-HT(2C) receptor mRNA expression in the posteromedial cortical amygdala (32%) and substantia nigra (35%) 2 h after the last drug administration, while rebound effects were also observed 48 h later. 5-HT(2C) receptor mRNA was only decreased in the substantia nigra at both 2 h (42%) and 48 h (54%) after the last haloperidol administration. Alterations in serotonin receptor expression in limbic system region such as the nucleus accumbens, hippocampus and lateral septal nucleus as well as the striatum may represent the specific regional targets that mediate the clinical effects of antipsychotics via the serotonin system.
本研究检测了大鼠连续36天给予氯氮平（1.5毫克/千克/天）和氟哌啶醇（2.0毫克/千克/天）后，其大脑中5-羟色胺（5-HT）（2A和2C）受体mRNA表达的区域变化。在末次给药后2小时或48小时处死大鼠，通过原位杂交检测5-HT（2A和2C）受体mRNA的表达及分布，以研究停药后的即时和延迟效应。停药2小时后，结果显示，与对照组相比，氯氮平给药显著降低了5-HT（2A）受体mRNA水平，主要降低部位为伏隔核（65%）、海马体（80%）、外侧隔核（61%）和纹状体（68%），而在48小时后，这些区域大多出现了反弹增加。相比之下，氟哌啶醇治疗组在停药后2小时或48小时，5-HT（2A）受体mRNA表达均未发现变化。氯氮平在末次给药后2小时，还降低了后内侧皮质杏仁核（32%）和黑质（35%）中5-HT（2C）受体mRNA的表达，48小时后也观察到了反弹效应。在末次给予氟哌啶醇后2小时（42%）和48小时（54%），黑质中5-HT（2C）受体mRNA仅出现降低。边缘系统区域如伏隔核、海马体、外侧隔核以及纹状体中5-羟色胺受体表达的改变，可能代表了通过5-羟色胺系统介导抗精神病药物临床效应的特定区域靶点。
