Dopamine, accumbens signaling & associative learning

描述（由申请人提供）：先前与药物使用相关的环境线索显著增强了寻求药物的行为。事实上，即使在长时间的禁欲之后，这些暗示的出现也会促进复发。一种治疗成瘾的潜在方法是减少对药物相关线索的行为控制。这需要理解环境刺激和药物奖励之间联系的本质；然而，关于这种关联是如何形成的，我们所知甚少。伏隔核在药物成瘾中起着至关重要的作用，因为它介导了滥用药物的强化作用。众所周知，环境线索对药物寻找的调节是通过伏隔核介导的。因此，我建议研究药物关联形成和表达过程中伏隔核内的神经变化。我将首先使用多单元阵列电生理学来评估在初始中性提示与静脉注射可卡因配对时神经元活动的变化。然后，我将使用快速扫描循环伏安法来评估这种关联过程中多巴胺的实时释放。这些研究的结果可能会促进旨在降低环境线索增强药物寻找能力的治疗。

DESCRIPTION (provided by applicant): Environmental cues previously paired with drug use significantly enhance drug-seeking behavior. In fact, presentation of such cues promotes relapse, even after long periods of abstinence. One potential treatment for addiction is to reduce the behavioral control of drug-associated cues. This requires understanding the nature of associations between environmental stimuli and drug reward; however, very little is known regarding how such associations are formed. The nucleus accumbens is critically involved in drug addiction, as it is known to mediate the reinforcing actions of abused drugs. It is known that modulation of drug seeking by environmental cues is mediated through the nucleus accumbens. I therefore propose to study neural alterations within the nucleus accumbens during the formation and expression of drug associations. I will first use multi-unit array electrophysiology to assess changes in neuronal activity while an initially neutral cue is paired with intravenous cocaine administration. I will then use fast-scan cyclic voltammetry to assess real time dopamine release during such associations. Results from these studies may promote treatments aimed at reducing the ability of environmental cues to enhance drug seeking.