Intracranial Drug Self-administration

颅内药物自我给药

• 批准号: 6680422
• 负责人: Roy Wise
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6680422
• 关键词: carbachol; endogenous opioid; gene induction /repression; injection /infusion; laboratory rat; neurogenetics; neuropharmacology; pharmacogenetics; psychopharmacology; reinforcer; self medication; tegmentum

Attempts to determine the neural circuitry where addictive drugs act to establish drug-seeking habits are aided by demonstration of drug self-administration directly into local brain regions. In the past year we have discovered that rats will learn to lever-press for injections of the cholinergic agent carbachol and the recently isolated endogenous ligand for the mu opiate receptor, endomorphin-1, directly into the ventral tegmental area, where the mesolimbic dopamine system originates. In each case we find evidence for differential effectiveness in the rostral and caudal portions of the ventral tegmental area. Endomorphin-1 was not self-administered into nucleus accumbens, where the mesolimbic dopamine system terminates. Animals would respond for neither substance when injected dorsal to the ventral tegmental area, ruling out diffusion up the cannula shaft to a distal site of action. These findings implicate projections from the pedunculopontine tegmental or dorsolateral tegmental pontine nuclei and from the arcuate nucleus in the neural network within which addictive drugs establish compulsive drug self-administration habits. We have begun to trace the evoked consequences of rewarding carbachol injections by assessing early immediate gene expression in distant brain regions.

通过直接表明药物自我给药直接到局部大脑区域的证明，试图确定令人上瘾的药物来建立寻求药物习惯的神经回路的尝试。在过去的一年中，我们发现，大鼠将学习对胆碱能剂卡尔巴乔尔的注射和最近隔离的内源性配体，用于Mu opiate受体内摩粒-1，直接进入腹侧换段区域，中腹多巴胺系统起源于腹膜。在每种情况下，我们都会发现证据表明腹侧对段区域的尾部和尾部部分有差异有效性。内啡肽1没有自我管理到伏隔核中，其中中断多巴胺系统终止。当向腹侧换段区域注射背侧时，动物都不会做出任何反应，从而排除了插管轴的扩散到远端作用部位。这些发现暗示了来自花梗te骨或背外侧侧侧pontine核以及神经网络中的弧形核的投影，在这些核心中，成瘾性药物在其中建立了强迫性药物自我管理习惯。我们已经开始通过评估遥远大脑区域的早期直接基因表达来追踪奖励卡巴乔的诱人后果。