NEURAL Mechanisms of Drug Seeking Behavior

可卡因依赖被视为一种慢性病，因为 高复发率，即使在长时间的 禁欲。因此，成功治疗可卡因依赖必须包括 预防复发。导致复发的因素包括诱因 可卡因本身或接触可卡因所产生的激励作用(如渴求) 与可卡因相关的线索(例如，用具、吸食可卡因的环境、 等)。最近的证据表明，不同的神经机制是 可卡因与可卡因线索的激励激励效应。领先理论 表明这些机制可能涉及单胺系统的变化，但 几乎没有做过什么研究来检验这一假说 单胺、5-羟色胺(5-羟色胺)参与。这项提议的目的是 目的是研究5-羟色胺系统在可卡因激励动机中的作用。这个 假说是增加5-羟色胺的大脑水平或刺激5-羟色胺 减少对可卡因的激励动机，而减少对 5-HT2受体会降低对可卡因的刺激动机。这些 假说将通过检查寻找可卡因的行为(即操纵者)来检验 在没有可卡因强化的情况下的反应被认为反映了 可卡因的动机)在给药后改变 5-羟色胺释放或刺激5-HT1a或5-HT2受体。的影响 这些药物对消除寻找可卡因的行为和恢复 可卡因配对线索的呈现将在无药物的动物身上进行检查 州政府。接下来，这些药物在可卡因联合给药和不可卡因联合给药的情况下的效果 关于恢复寻求可卡因的行为将进行审查。最后， 观察到的影响的行为特异性将通过比较它们来检验 药物对寻找蔗糖行为的影响。这些实验将 有助于阐明5-羟色胺参与可卡因激励动机的机制 并可能对开发治疗方法具有重要意义 可卡因依赖。

Cocaine dependence is viewed as a chronic condition because of the high incidence of relapse that occurs even after prolonged periods of abstinence. Thus, successful treatment of cocaine dependence must include prevention of relapse. Factors contributing to relapse include incentive motivational effects (e.g., craving) produced by cocaine itself or by exposure to cocaine-associated cues (e.g., paraphernalia, cocaine-taking environment, etc). Recent evidence suggests that different neural mechanisms underlie incentive motivational effects of cocaine versus cocaine cues. Leading theories suggest that these mechanisms likely involve changes in monoamine systems, yet little research has been done to test this hypothesis in regard to the involvement of the monoamine, serotonin (5-HT). The objective of this proposal is to examine the role of 5-HT systems in incentive motivation for cocaine. The hypotheses are that increasing 5-HT brain levels or 5-HT1A stimulation will decrease incentive motivation for cocaine, whereas decreasing stimulation of 5-HT2 receptors will decrease incentive motivation for cocaine. These hypotheses will be tested by examining cocaine-seeking behavior (i.e., operant responding in the absence of cocaine reinforcement that is thought to reflect motivation for cocaine) after administration of drugs that either alter serotonin release or stimulation of 5-HT1A or 5-HT2 receptors. The effects of these drugs on extinction of cocaine-seeking behavior and reinstatement by presentations of cocaine-paired cues will be examined in animals in a drug-free state. Next, effects of these drugs with and without cocaine co-administration on reinstatement of cocaine-seeking behavior will be examined. Finally, behavioral specificity of observed effects will be examined by comparing them to the effects of the drugs on sucrose-seeking behavior. These experiments will help to elucidate 5-HT mechanisms involved in incentive motivation for cocaine and will likely have important implications for developing treatments for cocaine dependence.