Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.
J Neurosci. 2011 May 18;31(20):7533-9. doi: 10.1523/JNEUROSCI.0172-11.2011.
Opponent process theory predicts that the first step in the induction of drug withdrawal is the activation of reward-related circuitry. Using the acoustic startle reflex as a model of anxiety-like behavior in rats, we show the emergence of a negative affective state during withdrawal after direct infusion of morphine into the ventral tegmental area (VTA), the origin of the mesolimbic dopamine system. Potentiation of startle during withdrawal from systemic morphine exposure requires a decrease in opiate receptor stimulation in the VTA and can be relieved by administration of the dopamine receptor agonist apomorphine. Together, our results suggest that the emergence of anxiety during withdrawal from acute opiate exposure begins with activation of VTA mesolimbic dopamine circuitry, providing a mechanism for the opponent process view of withdrawal.
拮抗过程理论预测，药物戒断诱导的第一步是奖励相关回路的激活。使用声发射反射作为大鼠焦虑样行为的模型，我们发现在腹侧被盖区（VTA）直接输注吗啡后戒断期间出现负性情绪状态，VTA 是中脑边缘多巴胺系统的起源。从系统给予吗啡暴露中戒断时的惊跳反应增强需要 VTA 阿片受体刺激的减少，并且可以通过给予多巴胺受体激动剂阿扑吗啡来缓解。总之，我们的结果表明，急性阿片类药物暴露戒断时出现焦虑始于 VTA 中脑边缘多巴胺回路的激活，为戒断的拮抗过程观点提供了一种机制。
