Kurokawa K, Narita M, Koshiya K, Hidaka K, Ohmori J, Satoh K
Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
Neuropsychopharmacology. 1997 Jul;17(1):27-33. doi: 10.1016/S0893-133X(97)00022-5.
The pharmacological characteristics of two benzamides, YM-43611, a potent and selective dopamine D3 and D4 antagonist, and YM-09151-2 (nemonapride), were compared with two reference antipsychotic agents, haloperidol and clozapine, in terms of modification of c-fos and related gene expression in the rat forebrain. After subcutaneous injection of YM-43611 (1 or 5 mg/kg), nemonapride (4 mg/kg), haloperidol (1 mg/kg), or clozapine (25 mg/kg), Fos immunocytochemistry was employed, and the distributions of Fos-like immunoreactive neurons were compared. As was the case for the two reference antipsychotics, the two benzamides enhanced c-Fos immunoreactivity in a number of forebrain regions. Specifically, like clozapine and nemonapride, YM-43611 significantly increased the number of immunoreactive cells in the nucleus accumbens shell and islands of Calleja. In contrast to clozapine and nemonapride, YM-43611 did not increase c-fos expression in the medial prefrontal cortex. Haloperidol and nemonapride elevated the number of positive cells in the striatum and nucleus accumbens core, whereas clozapine and YM-43611 did not. Clozapine increased the number of Fos-like immunoreactive cells in the lateral septal nucleus and the diagonal band nucleus, but YM-43611, nemonapride, and haloperidol did not. The present findings demonstrate that in comparison with three other drugs, YM-43611 has restricted effects on c-fos expression in the rat forebrain and is active primarily in the shell region of the nucleus accumbens and the islands of Calleja. The ability of YM-43611 to block D3 and D4 receptors may contribute to its unique actions on Fos induction.
将两种苯甲酰胺（强效选择性多巴胺D3和D4拮抗剂YM-43611以及YM-09151-2（奈莫必利））的药理学特性与两种参考抗精神病药物氟哌啶醇和氯氮平进行比较，观察它们对大鼠前脑c-fos及相关基因表达的影响。皮下注射YM-43611（1或5 mg/kg）、奈莫必利（4 mg/kg）、氟哌啶醇（1 mg/kg）或氯氮平（25 mg/kg）后，采用Fos免疫细胞化学方法，比较Fos样免疫反应性神经元的分布。与两种参考抗精神病药物一样，这两种苯甲酰胺增强了多个前脑区域的c-Fos免疫反应性。具体而言，与氯氮平和奈莫必利一样，YM-43611显著增加了伏隔核壳和Calleja岛中免疫反应性细胞的数量。与氯氮平和奈莫必利不同，YM-43611未增加内侧前额叶皮质中的c-fos表达。氟哌啶醇和奈莫必利增加了纹状体和伏隔核核心中的阳性细胞数量，而氯氮平和YM-43611则没有。氯氮平增加了外侧隔核和斜角带核中Fos样免疫反应性细胞的数量，但YM-43611、奈莫必利和氟哌啶醇没有。目前的研究结果表明，与其他三种药物相比，YM-43611对大鼠前脑c-fos表达的影响有限，主要作用于伏隔核壳区域和Calleja岛。YM-43611阻断D3和D4受体的能力可能有助于其对Fos诱导的独特作用。
