Role of CB1 receptors in cannabinoid-induced behavior

CB1 受体在大麻素诱导行为中的作用

• 批准号: 6790923
• 负责人: ERIK J SHANK
• 金额: $ 2.93万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6790923
• 关键词: Cannabis; GABA receptor; behavior test; behavioral /social science research tag; cannabinoid receptor; cannabinoids; central nervous system stimulants; central neural pathway /tract; drug abuse; gamma aminobutyrate; immunocytochemistry; injection /infusion; laboratory rat; neural information processing; neuroanatomy; nucleus accumbens; predoctoral investigator; psychomotor function; reinforcer; substance abuse related behavior

DESCRIPTION (provided by applicant): Marijuana is undoubtedly the most abused illicit drug in the world. The active ingredient in marijuana is delta-9-tetrahydrocannabinol, a member of the cannabinoid family for which there are two known receptors: CB1 (primarily CNS) and CB2 receptors. We will test the hypothesis that intra-VTA CB1 receptor activation with the synthetic agonist CP55, 940 can induce hyperactivity and that these receptors are located on GABA neurons within the VTA. Furthermore, we will test the hypothesis that normal GABA function is necessary for the behavioral effects of intra-VTA CP55, 940 infusion by selectively lesioning the GABA neurons within the VTA followed by subsequent CB1 agonist administration. The observation that acute microinfusion of the cannabinoid agonist CP55, 940 into the reward pathway results in hyperactivity would support the hypothesis that cannabinoids utilize similar circuitry as other abused drugs (e.g., cocaine, amphetamines, heroin, etc.) and suggest that the systemic effects of cannabinoids are a composite of actions in the mesoaccumbens and other pathways. These data are, therefore, critical in elucidating the rewarding/reinforcing effects of cannabinoid agonists.

描述（由申请人提供）： 无疑是世界上最受虐的非法药物。大麻中的活性成分是Delta-9-四氢大麻酚，这是大麻素家族的成员，其中有两个已知的受体：CB1（主要是CNS）和CB2受体。我们将检验以下假设：与合成激动剂CP55、940一起使用-VTA CB1受体激活可以诱导多动症，并且这些受体位于VTA内的GABA神经元上。此外，我们将测试以下假设：正常的GABA功能对于VTA内的GABA神经元进行选择性筛选，对Inta-VTA CP55和940输注的行为效应是必要的，然后是随后的CB1激动剂给药。大麻素激动剂CP55，940在奖励途径中的急性微灌注导致过度活跃的观察结果将支持以下假说：大麻素使用与其他滥用药物相似的电路，例如可卡因，苯丙胺，海洛因等），并建议对其他人的系统效应。因此，这些数据对于阐明大麻素激动剂的奖励/增强作用至关重要。