Fink-Jensen A, Ludvigsen T S, Korsgaard N
Health Care Discovery, Novo Nordisk A/S, Novo Nordisk Park, Måløv, Denmark.
Neurosci Lett. 1995 Jul 14;194(1-2):77-80. doi: 10.1016/0304-3940(95)11731-b.
The involvement of alpha 1-adrenergic and 5HT2-receptor blockade in the induction of Fos protein produced by the 'atypical' neuroleptic clozapine was investigated in the rat forebrain. The Fos protein immunohistochemical technique has been used to identify the anatomical substrate underlying the effects of typical and atypical neuroleptics. Clozapine (20 mg/kg) induced a significantly higher Fos protein immunoreactivity response in the medial prefrontal cortex and a significantly lower response in the dorsolateral striatum compared to the effect of haloperidol (1 mg/kg). The alpha 1-adrenergic antagonist prazosin (0.3 and 1.0 mg/kg) and the 5HT2 antagonist ritanserin (1 and 3 mg/kg) did not increase Fos protein immunoreactivity by themselves and did not mimic the clozapine response when co-administered with haloperidol (1 mg/kg). Consequently, this study suggests that neither alpha 1-adrenergic receptor blockade nor the 5HT2-receptor blockade accounts for the unique Fos protein expression pattern produced by clozapine.
在大鼠前脑中研究了α1 - 肾上腺素能和5HT2受体阻断在“非典型”抗精神病药物氯氮平诱导Fos蛋白产生过程中的作用。Fos蛋白免疫组织化学技术已被用于确定典型和非典型抗精神病药物作用的解剖学基础。与氟哌啶醇（1mg/kg）的作用相比，氯氮平（20mg/kg）在内侧前额叶皮质诱导出显著更高的Fos蛋白免疫反应性，而在背外侧纹状体诱导出显著更低的反应。α1 - 肾上腺素能拮抗剂哌唑嗪（0.3和1.0mg/kg）和5HT2拮抗剂利坦色林（1和3mg/kg）单独使用时不会增加Fos蛋白免疫反应性，与氟哌啶醇（1mg/kg）联合给药时也不会模拟氯氮平的反应。因此，本研究表明，α1 - 肾上腺素能受体阻断和5HT2受体阻断均不能解释氯氮平产生的独特Fos蛋白表达模式。
