A substantial amount of evidence suggests that 5-HT2A receptors mediate many of the behavioral effects of the hallucinogen LSD. This conclusion is based largely on the results of pharmacological studies which utilized compounds that lacked the ability to differentiate between the 5-HT2A and other members of the 5-HT2 family (5-HT2B, 5-HT2C) as well as other families of 5-HT receptors. However, a limited number of recent assessments of this question suggest that some aspects of LSD-invoked behavior may be mediated by 5-HT2C receptors as well. The intent of the present proposal is to directly assess the relative roles of 5-HT2A and 5HT2C receptors in the locomotor and discriminative stimulus effects of LSD employing selective 5-HT2A or 5-HT2C receptor ligands. In addition, we will map the anatomical circuitry upon which the behavioral effects of LSD are dependent using strategies that incorporate both immediate early gene expression in rat brain and direct site-specific microinfusion technologies.
