Reader T A, Ase A R, Huang N, Hébert C, van Gelder N M
Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Faculté de Médecine, Université de Montréal, Québec, Canada.
Neurochem Res. 1998 Jan;23(1):73-80. doi: 10.1023/a:1022405621365.
The effects of neuroleptic treatments on dopamine transporters and on dopamine receptors was investigated in the forebrain of adult rats treated for 21 days with either haloperidol, clozapine or saline. The dopamine D1 receptors, labeled with [3H]SCH23390, increased in nucleus accumbens, latero-dorsal rostral neostriatum and substantia nigra, after clozapine but not haloperidol. The dopamine D2 receptors, studied with [3H]raclopride, increased in nucleus accumbens and in dorso-lateral, ventro-medial and dorso-medial quadrants of the rostral neostriatum after either haloperidol or clozapine treatments, and also in latero-ventral rostral neostriatum but only after haloperidol. Haloperidol also up-regulated D2 receptors in rostral and caudal neostriatum, but clozapine produced a more uneven increase, especially in caudal neostriatum. In contrast, the densities of dopamine uptake sites, or transporters, labeled with [125I]RTI-121, remained unchanged after both neuroleptic treatments. The observation that dopamine transporters are resistant to treatments that modify D1 and D2 receptors indicates that these uptake sites can probably be ruled out as the target of neuroleptic drugs, and that dopamine receptor up-regulations can indeed occur independently of the densities of nerve endings at the terminal fields of innervation.
研究了用氟哌啶醇、氯氮平或生理盐水对成年大鼠进行21天治疗后，抗精神病药物治疗对多巴胺转运体和多巴胺受体在前脑的影响。用[3H]SCH23390标记的多巴胺D1受体，在氯氮平治疗后伏隔核、嘴侧背外侧新纹状体和黑质中增加，但氟哌啶醇治疗后未增加。用[3H]雷氯必利研究的多巴胺D2受体，在氟哌啶醇或氯氮平治疗后伏隔核以及嘴侧新纹状体的背外侧、腹内侧和背内侧象限中增加，在嘴侧腹外侧新纹状体中仅在氟哌啶醇治疗后增加。氟哌啶醇还上调了嘴侧和尾侧新纹状体中的D2受体，但氯氮平的增加更为不均匀，尤其是在尾侧新纹状体中。相比之下，用[125I]RTI-121标记的多巴胺摄取位点或转运体的密度，在两种抗精神病药物治疗后均保持不变。多巴胺转运体对改变D1和D2受体的治疗有抗性这一观察结果表明，这些摄取位点可能可以排除作为抗精神病药物的靶点，并且多巴胺受体上调确实可以独立于神经支配终末场的神经末梢密度而发生。
