5-HT1A receptor and hallucinogens

描述(由申请人提供)： 迷幻剂在我们的社会中的使用，特别是青少年和年轻人，仍然很普遍，因此是国家药物滥用研究所的一个主要兴趣。该项目的目的是阐明5-HTIA亚型的5-羟色胺能受体在致幻剂作用中的调节作用。这将使用行为和生化技术来确定[a]5-HT1A受体激动剂对苯乙胺迷幻剂DOM刺激控制的调制作用，[b]中缝背侧和内侧核团5-HT1A受体在DOM诱导刺激控制中的特定作用，[c]G蛋白激活在5-HTIA激动剂与DOM相互作用中的作用，以及[d]与5-HT1A配体有关的可能的5-羟色胺/谷氨酸能相互作用。这些研究中的行为变量将是DOM诱导的刺激控制。谷氨酸水平将通过体内微渗析和高效液相测定。[35S]GTPGammaS结合将用于确定5-HT1A受体刺激的分子机制。

DESCRIPTION (provided by applicant): The use of hallucinogens in our society, particularly adolescents and young adults, continues to be widespread and is thus a major interest of the National Institute on Drug Abuse. The aim of the proposed project is to elucidate the modulatory role of serotonergic receptors of the 5-HTIA subtype in the actions of hallucinogens. This will be accomplished using behavioral and biochemical techniques to determine [a] the modulatory effects of 5-HT1A receptor agonists on stimulus control by DOM, a phenethylamine hallucinogen, [b] the specific role of 5-HT1A receptors of the dorsal and medial raphe nuclei in DOM induced stimulus control, [c] the role of G protein activation in the interactions of 5-HTIA agonists with DOM, and [d] possible serotonergic/glutamatergic interactions as they relate to 5-HT1A ligands. The behavioral variable in these studies will be DOM-induced stimulus control. Glutamate levels will be determined by in vivo microdialysis and HPLC. [35S] GTPgammaS binding will be used to identify molecular mechanisms involved in 5-HT1A receptor stimulation.