NMDA receptors in cocaine reinforcement & relapse

可卡因强化中的 NMDA 受体

• 批准号: 6885439
• 负责人: Kelly A Carrigan-Simontacchi
• 金额: $ 4.01万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2005-12-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885439
• 关键词: NMDA receptors; behavioral /social science research tag; behavioral habituation /sensitization; cocaine; craving; cues; drug abuse; genetically modified animals; laboratory mouse; postdoctoral investigator; psychopharmacology; reinforcer; relapse /recurrence; self medication; substance abuse related behavior

DESCRIPTION (provided by applicant): The objective of the proposed studies is to investigate the role of NMDA receptors in the reinforcing effects of cocaine and the reinstatement of cocaine seeking behavior using a behavioral, pharmacological, and genetic approach. A mouse self-administration model is employed to assess cocaine self-administration behavior in mice with a deletion in the essential NR1 subunit of the NMDA receptor (NR1-KD). In Specific Aim I, cocaine self-administration behavior is assessed in NR1 mutant mice and wild-type littermate controls, Complete dose-effect functions for cocaine self-administration are generated on both fixed and progressive ratio schedules of reinforcement to compare the potency and reinforcing efficacy of cocaine in NR1 mutant and wild-type mice. Specific Aim II extends the findings of Specific Aim I and examines the role of NMDA receptors in cocaine relapse by assessing reinstatement of drug self-administration behavior in two models of human drug relapse: 1) following exposure to priming doses of cocaine or 2) following presentation of cues previously associated with cocaine administration in NR1 mutant mice and wild-type littermate controls. Collectively, the proposed studies will further our understanding of the role of glutamatergic mechanisms in the reinforcing effects of cocaine and reinstatement of cocaine-seeking behavior and may lead to new pharmacotherapeutic strategies for the treatment of drug dependence.

描述（由申请人提供）：拟议研究的目的是利用行为、药理学和遗传学方法研究 NMDA 受体在可卡因增强作用和恢复可卡因寻求行为中的作用。采用小鼠自我给药模型来评估 NMDA 受体 (NR1-KD) 必需 NR1 亚基缺失的小鼠的可卡因自我给药行为。在特定目标 I 中，在 NR1 突变小鼠和野生型同窝对照中评估可卡因自我给药行为，在固定和渐进比例强化方案上生成可卡因自我给药的完整剂量效应函数，以比较效力和强化效果可卡因对 NR1 突变型和野生型小鼠的功效。具体目标 II 扩展了具体目标 I 的发现，并通过评估两种人类药物复发模型中药物自我给药行为的恢复来检查 NMDA 受体在可卡因复发中的作用：1）暴露于启动剂量的可卡因后或 2）以下先前与 NR1 突变小鼠和野生型同窝对照小鼠中可卡因施用相关的线索的呈现。总的来说，拟议的研究将进一步加深我们对谷氨酸能机制在增强可卡因作用和恢复可卡因寻求行为中的作用的理解，并可能导致治疗药物依赖的新药物治疗策略。