NEURAL Mechanisms of Drug Seeking Behavior

可卡因依赖被视为一种慢性疾病，因为 复发率高，即使在长时间的 禁欲因此，可卡因依赖的成功治疗必须包括 预防复发。导致复发的因素包括： 激励效果（例如，渴望）由可卡因本身或接触可卡因产生 与可卡因相关的线索（例如，吸毒用具，吸食可卡因的环境， 等等）。最近的证据表明，不同的神经机制 可卡因与可卡因线索的激励作用。主要理论 这表明这些机制可能涉及单胺系统的变化， 几乎没有研究来测试这一假设， 参与的单胺，血清素（5-HT）。本提案的目的 研究5-HT系统在可卡因刺激动机中的作用。的 假设增加5-HT脑水平或5-HT 1A刺激将 减少可卡因的刺激动机，而减少 5-HT 2受体会降低可卡因的刺激动机。这些 假设将通过检查可卡因寻求行为（即，操作性 在没有可卡因强化的情况下做出反应， 可卡因的动机）， 5-羟色胺释放或5-HT 1A或5-HT 2受体的刺激。的影响 这些药物对可卡因寻求行为的灭绝和恢复， 可卡因配对线索的呈现将在无药物环境中的动物中进行检查。 状态接下来，这些药物与可卡因联合给药和不联合给药的效果 恢复寻求可卡因的行为将受到审查。最后， 观察到的效应的行为特异性将通过比较它们来检查 药物对寻求蔗糖行为的影响。这些实验将 有助于阐明5-HT机制参与可卡因的激励动机 并可能对开发治疗方法产生重要影响， 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.