Dopamine, accumbens signaling & associative learning

描述(由申请人提供)：以前与毒品使用配对的环境线索显著增强了寻求毒品的行为。事实上，即使在长期禁欲之后，呈现这样的暗示也会促进复发。一种治疗上瘾的潜在方法是减少对与药物相关的线索的行为控制。这需要了解环境刺激和药物奖励之间的关联的性质；然而，关于这种关联是如何形成的，人们知之甚少。伏隔核与药物成瘾密切相关，因为它是滥用药物强化作用的中介。众所周知，环境线索对药物寻找的调节是通过伏隔核来实现的。因此，我建议研究伏隔核在药物关联形成和表达过程中的神经变化。我将首先使用多单位阵列电生理学来评估神经元活动的变化，同时将最初的中性线索与静脉注射可卡因配对。然后，我将使用快速扫描循环伏安法来评估在这种关联过程中的实时多巴胺释放。这些研究的结果可能会促进旨在降低环境线索促进药物寻找的能力的治疗。

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.