Hallucinogens--Serotonergic Glutamatergic Interactions

本研究的目标是结合和整合行为学和生物化学技术：(1)进一步表征吲哚胺和苯乙胺致幻剂在药物诱导刺激控制中的5 -羟色胺-谷氨酸能相互作用；(2)确定这种相互作用的分子机制。因此，人们普遍认为，使用药物鉴别的行为结果在人类中具有显著的主观相关性，将与各种生物化学疗效指标（如神经递质在体内的释放和NMDA受体的可逆分子修饰）进行关联和比较。本研究将利用微注射和微透析技术在细胞水平上创造和研究致幻剂施用过程中的条件。该研究还将利用药物歧视作为一种将上述条件与大鼠行为联系起来的方法。致幻剂是青少年和年轻人的一个重大保健问题，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，阐明致幻剂的作用机制可能有助于理解精神分裂症和其他精神疾病。

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.