Burger L Y, Martin-Iverson M T
Department of Psychiatry, Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Canada.
Brain Res. 1994 Mar 14;639(2):228-32. doi: 10.1016/0006-8993(94)91734-5.
In rats exhibiting behavioural sensitization after daily cocaine (10 mg/kg, i.p.) injections, the occupation of D1 and D2 dopamine receptors by dopamine, measured as protection from N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) receptor denaturation, was increased by about 100% compared to animals receiving cocaine in a treatment regimen that produced behavioural tolerance. Co-administration with nimodipine, an agent that blocks the impulse-dependent increase in synaptic concentrations of dopamine caused by cocaine, not only blocked sensitization but also blocked the increase in occupation of receptors. These findings strongly support the hypothesis that enhanced dopamine release and subsequent interaction with dopamine receptors is a substrate for behavioural sensitization to cocaine and have implications for the pharmacotherapy of cocaine abuse.
在每日腹腔注射可卡因（10毫克/千克）后出现行为敏化的大鼠中，通过测量多巴胺对N - 乙氧羰基 - 2 - 乙氧基 - 1,2 - 二氢喹啉（EEDQ）受体变性的保护作用来评估，多巴胺对D1和D2多巴胺受体的占据情况，与接受产生行为耐受的治疗方案的可卡因的动物相比增加了约100%。与尼莫地平共同给药，尼莫地平是一种阻断可卡因引起的依赖冲动的多巴胺突触浓度增加的药物，不仅阻断了敏化，还阻断了受体占据的增加。这些发现有力地支持了以下假设：多巴胺释放增强以及随后与多巴胺受体的相互作用是对可卡因行为敏化的基础，并且对可卡因滥用的药物治疗具有启示意义。
