D'Souza U, McGuffin P, Buckland P R
Department of Psychological Medicine, University of Wales College of Medicine, Cardiff, UK.
Neuropharmacology. 1997 Nov-Dec;36(11-12):1689-96. doi: 10.1016/s0028-3908(97)00163-9.
A range of antipsychotic drugs, both "typical" and "atypical", was administered to rats over a time course and at several different dosages. The mRNA levels of dopamine D1, D2 and D3 receptor were measured in either whole brain or dissected brain regions. D3 receptor mRNA was up-regulated in whole brain by clozapine (10 and 30 but not 3 mg/kg/day), sulpiride (50 and 100 but not 20 mg/kg/day). haloperidol (3 but not 1 or 0.3 mg/kg/day), flupenthixol (3 but not 1 or 0.3 mg/kg/day), pimozide (4.5 but not 1.5 or 0.5 mg/kg/day) and loxapine (1.2 and 4 mg/kg/day but not 0.4 mg/kg/day). Sulpiride (100 mg/kg/day), clozapine (30 mg/kg/ day) and haloperidol (3 mg/kg/day) all up-regulated the D3 receptor mRNA in nucleus accumbens and olfactory tubercles but not striatum. D1 and D2 receptor mRNA was up-regulated in whole brain by haloperidol and loxapine only, and in the case of haloperidol this was localized to striatum and prefrontal cortex. Haloperidol, clozapine and sulpiride all down-regulated D1 mRNA in hippocampus and additionally haloperidol and sulpiride down-regulated it in the cerebellum. This work shows that all the drugs tested up-regulated D3 receptor, but effects on D1 and D2 receptors were less general.
在一段时间内，给大鼠施用了一系列“典型”和“非典型”抗精神病药物，并设置了几种不同剂量。在全脑或解剖后的脑区中测量多巴胺D1、D2和D3受体的mRNA水平。氯氮平（10和30mg/kg/天，但3mg/kg/天无效）、舒必利（50和100mg/kg/天，但20mg/kg/天无效）、氟哌啶醇（3mg/kg/天，但1或0.3mg/kg/天无效）、三氟噻吨（3mg/kg/天，但1或0.3mg/kg/天无效）、匹莫齐特（4.5mg/kg/天，但1.5或0.5mg/kg/天无效）和洛沙平（1.2和4mg/kg/天，但0.4mg/kg/天无效）可使全脑中D3受体mRNA上调。舒必利（100mg/kg/天）、氯氮平（30mg/kg/天）和氟哌啶醇（3mg/kg/天）均可使伏隔核和嗅结节中的D3受体mRNA上调，但对纹状体无效。仅氟哌啶醇和洛沙平可使全脑中D1和D2受体mRNA上调，就氟哌啶醇而言，这种上调定位于纹状体和前额叶皮质。氟哌啶醇、氯氮平和舒必利均可使海马体中的D1 mRNA下调，此外，氟哌啶醇和舒必利还可使小脑中的D1 mRNA下调。这项研究表明，所有测试药物均可使D3受体上调，但对D1和D2受体的影响则不那么普遍。
