Semba J, Sakai M, Miyoshi R, Mataga N, Fukamauchi F, Kito S
University of Air, Chiba, Japan.
Neurochem Int. 1996 Oct;29(4):435-42. doi: 10.1016/0197-0186(95)00156-5.
The regional difference in the expression of c-fos mRNA induced by typical and atypical antipsychotics was determined in prefrontal cortex, striatum, N. accumbens and lateral septum in rats by in situ hybridization. Two typical antipsychotics, haloperidol (2 mg/kg) and fluphenazine (2 mg/kg), and three atypical antipsychotics, (-)sulpiride (100 mg/kg), clozapine (20 mg/kg) and OPC-14597 (40 mg/kg), were used. Brains were fixed with 4% paraformaldehyde 45 min after drug administration (i.p.). Brain sections of 30 microns-thickness were made in a cryostat and hybridized with 35S-labelled for c-fos oligonucleotide probe. These sections were apposed to X-ray films and the autoradiograms were semi-quantitatively analysed by computer-assisted densitometry. All antipsychotics used increased c-fos mRNA expression in N. accumbens shell, a region of the forebrain associated with limbic systems. On the other hand, two typical antipsychotics (haloperidol and fluphenazine) that cause a high incidence of acute motor side effects increased the expression of c-fos mRNA in the dorsolateral striatum, an extrapyramidal region primarily involved in motor control. Only clozapine induced c-fos mRNA in the medial prefrontal cortex and lateral septum. These results strongly suggest that the shell region of N. accumbens may be a common site of therapeutic action of antipsychotics.
通过原位杂交技术，测定了典型和非典型抗精神病药物诱导的大鼠前额叶皮质、纹状体、伏隔核和外侧隔核中c-fos mRNA表达的区域差异。使用了两种典型抗精神病药物，氟哌啶醇（2mg/kg）和氟奋乃静（2mg/kg），以及三种非典型抗精神病药物，（-）舒必利（100mg/kg）、氯氮平（20mg/kg）和OPC-14597（40mg/kg）。给药（腹腔注射）45分钟后，用4%多聚甲醛固定大鼠大脑。在低温恒温器中制作30微米厚的脑切片，并用35S标记的c-fos寡核苷酸探针进行杂交。将这些切片与X射线胶片相对放置，通过计算机辅助密度测定法对放射自显影片进行半定量分析。所有使用的抗精神病药物均增加了伏隔核壳区（与边缘系统相关的前脑区域）的c-fos mRNA表达。另一方面，两种导致急性运动副作用发生率较高的典型抗精神病药物（氟哌啶醇和氟奋乃静）增加了背外侧纹状体（主要参与运动控制的锥体外系区域）的c-fos mRNA表达。只有氯氮平诱导了内侧前额叶皮质和外侧隔核中的c-fos mRNA表达。这些结果强烈表明，伏隔核壳区可能是抗精神病药物治疗作用的共同位点。
