Mechanisms of Cocaine Induced Long-term Potentiation

可卡因诱导长时程增强的机制

• 批准号: 6878935
• 负责人: ANTONELLO BONCI
• 金额: $ 24.11万
• 依托单位: ERNEST GALLO CLINIC AND RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6878935
• 关键词: AMPA receptors; behavioral habituation /sensitization; brain electrical activity; cell cell interaction; cell population study; chemical structure function; cocaine; immunocytochemistry; intermolecular interaction; laboratory rat; long term potentiation; neural plasticity; neural transmission; neurogenetics; neurons; neuropharmacology; neuroregulation; phosphorylation; receptor coupling; receptor expression; second messengers; synapses; tegmentum; voltage /patch clamp; western blottings

DESCRIPTION (provided by applicant): The goal of the present proposal is to understand the cellular and synaptic events through which cocaine induces long-term plasticity at excitatory synapses in the ventral tegmental area (VTA) after a single in vivo exposure. The VTA considered to play a central role in the initiation of drug-related behaviors such as behavioral sensitization, but the cellular mechanisms that underlie the initiation of such behavioral phenomena are still obscure. Our preliminary data suggest that a single injection of cocaine produces a long-term potentiation (LTP) of AMPA-receptor-mediated post-synaptic currents in the VTA. Furthermore, when mice were challenged with a second injection of cocaine, they displayed context-dependent behavioral sensitization. Further, both cocaine-induced LTP and context-dependent behavioral sensitization are blocked by the NMDA receptor antagonist MK-801. Our first goal is to determine whether the expression of cocaine-induced LTP involves a change in AMPA receptor number, function, or both. Second, we will perform intra-VTA in vivo injections to understand whether intra-VTA injections of cocaine are sufficient for cocaine to induce LTP, and to define the receptors and second messengers involved in producing the cocaine-induced LTP. Third, we will use an in vitro model to study which receptors in the VTA are involved in producing the cocaine-mediated long-term potentiation. Fourth, we will determine whether such cocaine dependent LTP also occurs in tertiary cells, a group of VTA neurons whose function is still unknown. Our long-term goal is to understand the complete sequence of cellular and molecular events through which cocaine produces LTP at AMPA receptors in the VTA and the subsequent initiation of behavioral sensitization.

描述（由申请人提供）：本提案的目标是