PERIADOLESCENT MDMA--LONG TERM NEUROBEHAVIORAL EFFECTS

尽管滥用药物的社会趋势发生在青少年和 成年人、男性和女性，对滥用药物的基础研究很少 以年龄和性别为自变量进行调查。尽管有调查结果 精神刺激剂3，4-亚甲基二氧基甲基苯丙胺(MDMA， 摇头丸)，具有典型的药物神经生物学特征 改变可卡因的增强效果，亚甲基二氢叶酸的作用 还没有对可卡因的强化进行调查。因此，总体目标是 目前实验的目的是检验年龄和年龄的意义 性别在MDMA长期神经行为影响中的作用。具体的 目的如下：1)记录5-羟色胺(5-HT)和谷氨酸 青春期和成年、男性和女性的脑耗竭 暴露于MDMA的大鼠；2)检验MDMA将增加的假设 强化作用；3)观察神经传导功能。 通过记录对MDMA预暴露的行为反应 可卡因自身用5HT1b、5HT2C或多巴胺D1受体激动剂 给药，以及伏隔核和核内神经递质水平 可卡因自身给药前后腹侧被盖区。 总之，拟议的实验将提供关于年龄和 1)药物相关神经毒性和行为的性别差异 功能障碍；2)5-羟色胺功能障碍对补肾功能的长期影响 可卡因的特性；3)5-羟色胺的神经毒性作用。 中脑边缘系统中的单胺能相互作用。这些 调查可能有助于深入了解兴奋剂的病因学 依赖并可能导致精神刺激剂的新药物疗法 上瘾。

Despite societal trends for drug abuse to occur in adolescents and adults, men and women, basic research on drugs of abuse is seldom conducted with age and gender as independent variables. Despite findings that the psychostimulant, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), has neurobiological characteristics typical of drugs that alter the reinforcing efficacy of cocaine, the effects of MDMA on cocaine reinforcement have not been investigated. Thus, the overall aim of the present experiments is to examine the significance of age and gender in the long-term neurobehavioral effects of MDMA. The specific aims are as follows: 1) to record serotonin (5HT) and glutamate depletion in the brain of periadolescent and adult, male and female rats, exposed to MDMA; 2) to test the hypothesis that MDMA will increase the reinforcing effects; and 3) to examine neurotransmission following MDMA pre-exposure by recording behavioral responses to pretreatment with 5HT1B, 5HT2C or dopamine D1 receptor agonists before cocaine self- administration, and neurotransmitter levels in the nucleus accumbens and ventral tegmental area before and during cocaine self-administration. Together the proposed experiments will provide information on age and gender differences in 1) drug-related neurotoxicity and behavioral dysfunction; 2) the long-term effects 5HT dysfunction on the reinforcing properties of cocaine; and 3) the effects of 5HT neurotoxicity on monoaminergic interactions in the mesolimbic system. These investigations may provide insight into the etiology of stimulant dependence and may lead to novel pharmacotherapies for psychostimulant addiction.