5-HT1A receptor and hallucinogens

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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.