COCAINE WITHDRAWAL AND 5 HT3 RECEPTORS

研究表明，中枢5-羟色胺（5-HT 3：血清素） 受体调节：（1）多巴胺（DA）介导的行为，（2） 中皮质边缘DA释放，和（3）戒断综合征相关 滥用药物。本申请提出检查 5-HT 3受体在调节行为和神经化学变化中的作用 通过渗透性微型泵持续注入可卡因而产生。 连续注射可卡因是一种强迫性的动物模型， 大量吸食可卡因该提案假设， 连续可卡因给药导致5-HT 3 受体调节DA神经传递和DA介导的行为。这 将在几个不同的层面审查监管能力的下降 分析，以获得这些变化的综合情况， 受体。具体地，本申请将检查在以下方面的改变： 5-HT 3受体激动剂和拮抗剂调节DA的能力 从纹状体、脑桥核的脑切片中释放， 前额叶皮层，和5-HT 3受体激动剂的能力变化 和拮抗剂来调节行为。目前的实验不会 只是进一步阐明了5-HT 3受体在可卡因滥用中的作用， 也可能导致更全面地了解其功能意义 其他精神疾病滥用可卡因导致焦虑/情绪 精神障碍、抑郁症和精神病。中枢5-羟色胺与 在所有这些条件下。因此，更全面地了解行为 5-HT 3系统的神经药理学不仅有助于我们理解 其他精神疾病，但也可能导致改善 各种精神疾病的药物治疗。

Research indicates that central 5-hydroxytryptamine(3) (5-HT3: serotonin) receptors regulate: (1) dopamine (DA) mediated behaviors, (2) mesocorticolimbic DA release, and (3) the withdrawal syndrome associated with drugs of abuse. The present application proposes to examine the role of 5-HT3 receptors in regulating the behavioral and neurochemical changes engendered by the continuous infusion of cocaine via an osmotic minipump. The continuous infusion of cocaine is an animal model of compulsive, binge-like, high-dose cocaine abuse. The proposal hypothesizes that continuous cocaine administration produces a decreased ability of 5-HT3 receptors to regulate DA neurotransmission and DA-mediated behaviors. This decreased regulatory capacity will be examined at several different levels of analyses to obtain an integrated picture of the changes in these receptors. Specifically, the present application will examine changes in the ability of 5-HT3 receptor agonists and antagonists to regulate DA release in brain slices from the striatum, nucleus accumbens, and prefrontal cortex, and changes in the ability of 5-HT3 receptor agonists and antagonists to regulate behavior. The present experiments will not only further elucidate the role of 5-HT3 receptors in cocaine abuse, but may also result in a fuller understanding of their functional significance for other psychiatric conditions. Cocaine abuse results in anxiety/mood disorders and depression, and psychosis. Central 5-HT have been implicated in all of these conditions. Thus, a fuller understanding of the behavioral neuropharmacology of 5-HT3 systems may not only aid in our understanding of other psychiatric conditions, but may also result in improved pharmacotherapies for a variety of psychiatric conditions.