Shilling P D, Kelsoe J R, Segal D S
Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla 92093-0603, USA.
Neurosci Lett. 1997 Nov 7;236(3):131-4. doi: 10.1016/s0304-3940(97)00768-4.
Converging evidence supports a significant role for dopamine (DA) in the development of behavioral sensitization and it has been suggested that changes in either DA transporter (DAT) or D2 autoreceptors contribute to the effects of stimulant treatment. To determine if alterations in DAT or D2 autoreceptor mRNA are long-lasting and parallel the time course of amphetamine (AMPH)-induced behavioral sensitization we performed the following experiment. Two groups of rats were used for mRNA analysis by in situ hybridization. They were given either single daily injections of saline or AMPH (2.5 mg/kg) for 5 days and sacrificed 7 days later. Two groups pretreated in a similar manner were used to test for behavioral sensitization. Pretreatment with AMPH which resulted in a sensitization response profile after AMPH challenge also produced a significant up-regulation of DAT mRNA in both the ventral tegmental area (VTA) (P = 0.01) and substantia nigra (SN) (P < 0.05) compared to the saline controls, whereas there were no significant group differences in D2 mRNA in either the SN or the VTA. The possible role of these changes in behavioral sensitization is discussed.
越来越多的证据支持多巴胺(DA)在行为敏化发展中起重要作用,并且有人提出多巴胺转运体(DAT)或D2自身受体的变化有助于兴奋剂治疗的效果。为了确定DAT或D2自身受体mRNA的改变是否持久并与苯丙胺(AMPH)诱导的行为敏化的时间进程平行,我们进行了以下实验。两组大鼠用于原位杂交mRNA分析。它们每天单次注射生理盐水或AMPH(2.5mg/kg),共5天,并在7天后处死。以类似方式预处理的两组用于测试行为敏化。与生理盐水对照组相比,用AMPH预处理导致AMPH激发后产生敏化反应,同时在腹侧被盖区(VTA)(P = 0.01)和黑质(SN)(P <0.05)中DAT mRNA均显著上调,而在SN或VTA中,D2 mRNA在两组之间无显著差异。讨论了这些变化在行为敏化中的可能作用。