Hallucinogens--Serotonergic Glutamatergic Interactions

致幻剂--血清素谷氨酸相互作用

• 批准号: 6515904
• 负责人: MEREDITH J REGINA
• 金额: $ 2.93万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6515904
• 关键词: 2,5 dimethoxy 4 methylamphetamine; NMDA receptors; behavior test; biochemistry; gas chromatography mass spectrometry; glutamates; hallucinogens; immunoprecipitation; indoleamine; intermolecular interaction; laboratory rat; lysergic acid diethylamide; male; microdialysis; microinjections; molecular dynamics; neurotransmitter antagonist; phenylethylamines; preference; psychopharmacology; serotonin; stimulus /response; substance abuse related behavior

The objectives of the present proposal are to combine and integrate behavioral and biochemical techniques (i) to characterize further the serotonergic-glutamatergic interaction in drug-induced stimulus control by indoleamine and phenethylamine hallucinogens and (ii) to determine the molecular mechanisms involved in this interaction. Thus, behavioral results using drug discrimination, which is widely believed to have significant subjective correlates in humans, will be correlated and compared with various biochemical measures of efficacy such as the in vivo release of neurotransmitter and reversible molecular modifications of the NMDA receptor. This study will utilize techniques of microinjection and microdialysis to create and study conditions at the cellular level present during administration of hallucinogen. The study will also utilize drug discrimination as a way to correlate said conditions with behavior in rats. Hallucinogens are a significant health care problem in adolescents and young adults, with the use of these drugs surpassing that of cocaine. Furthermore, the ability of some hallucinogens to mimic human psychosis suggests that an elucidation of the mechanisms of action of hallucinogenic drugs may contribute to an understanding of schizophrenia and other psychotic disorders.

本提案的目标是联合收割机和整合行为和生化技术（i）进一步表征药物诱导的刺激控制吲哚胺和苯乙胺致幻剂的神经能-神经元能相互作用和（ii）确定参与这种相互作用的分子机制。因此，使用药物辨别的行为结果（其被广泛认为在人类中具有显著的主观相关性）将与功效的各种生物化学测量（例如神经递质的体内释放和NMDA受体的可逆分子修饰）相关联并进行比较。本研究将利用显微注射和微透析技术，在细胞水平上创造和研究致幻剂给药期间存在的条件。该研究还将利用药物辨别作为将所述条件与大鼠行为相关联的一种方式。致幻剂是青少年和年轻人的一个重要卫生保健问题，这些药物的使用超过了可卡因。此外，一些致幻剂模仿人类精神病的能力表明，阐明致幻药物的作用机制可能有助于理解精神分裂症和其他精神障碍。