DOPAMINE SENSITIZATION BY MOTIVATED BEHAVIORS

描述：（改编自研究者摘要） 神经元的细胞特性（即，致敏）被认为是 一种机制介导个人继续吸毒和复吸 他们已经戒断了毒品然而，这就留下了一个问题， 是什么导致在诱导前开始和维持药物使用 重复使用药物后的致敏性。像滥用药物，性 行为将激活雌性仓鼠的中脑多巴胺通路。 先前的性经验会使多巴胺对性的反应敏感， 互动，并产生行为敏感的初始介绍， 安非他明（即，交叉致敏）。的 该项目的长期目标将是比较解剖学和 在细胞水平上，动机性行为和滥用药物的程度 多巴胺通路致敏的常见机制。有4个具体 这个项目的目标。前两个目标将分析的性质， 使用微透析测量性经验产生的致敏作用， 使用c-Fos的细胞外多巴胺浓度和突触后激活 免疫细胞化学细胞外多巴胺致敏的持续性 丘脑核的反应，对新环境的反应， 将研究安非他明治疗的交叉致敏作用。第三个目标是 研究介导致敏多巴胺反应的突触前机制， 微透析研究性经验对女性的潜在长期影响 自体受体功能和多巴胺转运蛋白将在本研究中进行探讨。 瞄准第四个目标将确定是否有持久的突触后 性经历后的变化一个实验将测试是否有 在性经验的多巴胺D1受体内化减少 女性第二个实验将评估cAMP积累对 D1受体的激活是先前性经验的函数。最终 目的是研究多巴胺D1和D2受体可能的长期变化 性经验之后。总之，这些实验将为 未来的研究将比较与神经系统相关的行为所产生的神经变化， 动物的自然史与反复暴露于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.