STRESSOR CONTROLLABILITY, DRUGS OF ABUSE, AND SEROTONIN

描述：（改编自研究者摘要） 对滥用药物的反应存在个体差异，但这些差异的原因 差异没有得到很好的理解。最近的“压力”经历是一个 已知在人类和动物中增强药物奖励过程的因素， 但压力的关键方面和涉及的神经机制 并不完全清楚。拟议的研究探讨了程度的作用 个体对压力源的行为控制 调节枯萎的压力将改变药物的反应性，并侧重于 应激诱导的脊髓背角5-HT能神经元的敏感化 中缝核（DRN）作为中介。待检验的假设是：（1） 不可控制的（但不是可控的）应激物使DRN 5-HT神经元敏感， 一段时间，导致投射区5-HT过度释放 （2）5-HT在丘脑腹外侧核（NAc）释放; 和/或内侧前额叶皮质（mPFC）的神经元从DRN投射 增加这些区域产生的DA的细胞外水平 室旁核释放的5-HT增加 血皮质酮（CORT）水平; 4）激活DRN 5-HT的药物 神经元（例如，吗啡）除了作用于大脑的奖赏结构， 因此在NAc/mPFC和CORT中产生更高水平的细胞外DA 对于最近接受过无法控制的压力的受试者，血液中的浓度; 4） 无法控制的（但不可控的）压力源将因此增强 依赖于NAc/mPFC DA和/或CORT的药物行为反应， 对于激活DRN 5-HT神经元的药物将发生增强作用。调节 位置偏好和运动激活是要检查的行为， 吗啡、安非他明、海洛因、尼古丁、可卡因和乙醇都是毒品 这将被测试。

DESCRIPTION: (Adapted from the Investigator's Abstract) There are large individual differences in reactivity to drugs of abuse, but the causes of these differences are not well understood. The recent experience of "stress" is a factor known to potentiate drug reward processes in both humans and animals, but the aspects of stress that are critical and the neural mechanisms involved are not fully known. The proposed research explores the role of the degree of behavioral control that the individual has over the stressor as a feature modulating wither the stressor will alter drug reactivity, and focuses on stressor-induced sensitization of serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN) as a mediator. The hypothesis to be tested is that 1) uncontrollable (but not controllable) stressors sensitize DRN 5-HT neurons for a period of time, leading to exaggerated release of 5-HT in projection regions when the neurons are activated; 2) 5-HT released in the nucleus accumbens (NAc) and/or medial prefrontal cortex (mPFC) by neurons projecting from the DRN increases the extracellular level of DA in the these regions that is produced by drugs of abuse; 3) 5-HT released in the paraventricular nucleus increases the blood levels of corticosterone (CORT); 4) Drugs that activate DRN 5-HT neurons (e.g., morphine) in addition to acting on brain reward structures, will therefore produce greater levels of extracellular DA in the NAc/mPFC and CORT in blood for subjects that have recently received uncontrollable stressors; 4) uncontrollable (but not controllable) stressors will therefore potentiate behavioral responses to drugs that depend on NAc/mPFC DA and/or CORT, and this potentiation will occur for drugs that activate DRN 5-HT neurons. Conditioned place preference and locomotor activation are the behaviors to be examined, and morphine, amphetamine, heroin, nicotine, cocaine, and ethanol are the drugs that will be tested.