DOPAMINE SENSITIZATION BY MOTIVATED BEHAVIORS

描述：(改编自《调查员摘要》)长期变化 神经元的细胞特性(即敏化)一直被认为是 一种调节个人持续药物滥用和复发的机制 已经戒毒的人。然而，这就留下了一个问题： 是什么导致了诱导前药物使用的启动和维持 反复使用药物后的致敏作用。就像滥用毒品，性行为 行为将激活雌性仓鼠的中隔伏隔神经多巴胺通路。 之前的性生活经历会使多巴胺对性行为的反应敏感 互动并产生对初始演示文稿的行为敏感化 安非他明(即交叉致敏)在其他药物幼稚的动物中的作用。这个 这个项目的长期目标将是在解剖学和 细胞水平动机行为和滥用药物的程度 多巴胺通路敏化的常见机制。有4个具体的 这个项目的目标。前两个目标将分析 使用微渗析测量的性经验产生的敏感化 细胞外多巴胺浓度与c-Fos的突触后激活 免疫细胞化学。细胞外多巴胺敏化的持久性 伏隔核的反应，对新环境的反应， 将研究苯丙胺治疗的交叉增敏作用。第三个目标是 探讨突触前介导致敏的多巴胺反应的机制 微渗析研究。性经验对健康的潜在长期影响 本文将探讨自身受体的功能和多巴胺转运体。 瞄准。第四个目标将决定是否存在持久的突触后 性体验之后的变化。一项实验将测试是否存在 性经验患者多巴胺D_1受体内在化减少 女性。第二个实验将评估cAMP积累对 D1受体的激活与先前的性经验有关。决赛 AIM将研究多巴胺D1和D2受体可能的长期变化 追随性体验。总之，这些实验将为 未来的研究比较了与行为相关的神经变化 动物的自然史与反复接触药物引起的动物的自然史 虐待。

DESCRIPTION: (Adapted from the Investigator's Abstract) Long-term changes in the cellular properties of neurons (i.e., sensitization) has been thought to be one mechanism mediating both continued drug abuse and relapse in individuals who have been abstinent from drug use. However, this leaves the question of what leads to the initiation and maintenance of drug use prior to the induction of sensitization following repeated use of drugs. Like drugs of abuse, sexual behavior will activate the mesoaccumbens dopamine pathway in female hamsters. Prior sexual experience will sensitize the dopamine response to sexual interactions and produce behavioral sensitization to the initial presentation of amphetamine (i.e., cross-sensitization) in otherwise drug-naive animals. The long-term goal of this project will be to compare at the anatomical and cellular levels the degree to which motivated behaviors and drugs of abuse have common mechanisms of sensitization of dopamine pathways. There are 4 specific aims of this project. The first two aims will analyze the properties of sensitization produced by sexual experience using microdialysis measurements of extracellular dopamine concentrations and postsynaptic activation using c-Fos immunocytochemistry. The persistence of sensitization of extracellular dopamine responses in the nucleus accumbens, responsivity to a novel environment, cross-sensitization to amphetamine treatment will be studied. The third aim is to examine presynaptic mechanisms mediating the sensitized dopamine response in microdialysis studies. Potential long-term effects of sexual experience on autoreceptor function and the dopamine transporter will be explored in this aim. The fourth aim will determine whether there are enduring postsynaptic changes following sexual experience. One experiment will test whether there is a decrease in dopamine D1 receptor internalization in sexually-experienced females. A second experiment will assess responsivity of cAMP accumulation to activation of D1 receptors as a function of prior sexual experience. A final aim will examine possible long-term changes in dopamine D1 and D2 receptors following sexual experience. Together, these experiments will pave the way for future studies comparing neural changes produced by behaviors relevant to the natural history of animals with those induced by repeated exposure to drugs of abuse.