PERIADOLESCENT MDMA--LONG TERM NEUROBEHAVIORAL EFFECTS

青春期摇头丸——长期神经行为影响

• 批准号: 6174605
• 负责人: KYLE J. FRANTZ
• 金额: $ 3.24万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6174605
• 关键词: 3,4 methylenedioxymethamphetamine; age difference; animal puberty; behavior test; behavioral /social science research tag; cocaine; drug abuse; gender difference; glutamates; injection /infusion; laboratory rat; mature animal; mesencephalon; microdialysis; neural transmission; neuropsychology; neurotoxicology; nucleus accumbens; prosencephalon; psychopharmacology; reinforcer; serotonin; substance abuse related behavior; tegmentum

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.

尽管青少年和青少年中存在药物滥用的社会趋势， 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。尽管发现 精神兴奋剂，3，4-亚甲二氧基甲基苯丙胺（MDMA， 摇头丸），具有典型的药物神经生物学特征， 改变可卡因的强化功效，MDMA对 可卡因的强化作用尚未得到研究。 因此，总体目标 本实验的目的是研究年龄和 MDMA长期神经行为影响中的性别。 具体 目的：1）记录5-羟色胺（5-HT）和谷氨酸 青春期前和成年男性和女性大脑中的消耗 大鼠，暴露于MDMA; 2）测试假设，MDMA将增加 强化作用; 3）检查以下神经传递 MDMA预暴露，通过记录对预处理的行为反应， 可卡因自身给药前使用5 HT 1B、5 HT 2C或多巴胺D1受体激动剂 给药，和神经递质水平在脑桥核和 可卡因自我给药前和给药期间的腹侧被盖区。 这些拟议的实验将共同提供关于年龄和 1）药物相关神经毒性和行为 5-HT功能障碍的长期影响 可卡因的性质;和3）5 HT神经毒性的影响， mesolimbic系统中的单胺能相互作用。 这些 调查可以提供深入了解兴奋剂的病因 依赖，并可能导致新的药物治疗精神兴奋剂 成瘾