The serotonin 2A receptor (5HT2AR) has been established as the key receptor to be involved in the actions of hallucinogens. Our group has recently reported hallucinogens induce a unique gene expression profile in the somatosensory cortex (SSC) of mice. This unique gene expression profile is distinct from that studied upon treatment with non-hallucinogens. I hypothesize the signal transduction processes involved in inducing rthisspecific neuronal response, are integral to the mechanisms of actions of hallucinogens. Based on preliminary studies, I propose the hallucinogen-specific neuronal responses elicited result from a direct effect on 5HT2AR on cortical neurons in SSC. I will characterize the 5HT2AR mediated signaling pathways and study the circuitry involved. This study will use quantitative high throughput gene expression profiles, primary cortical cultures and region-specific rescue 5HT2AR knock-out mice that have already been generated, to explore the molecular basis and neuronal circuitry underlying the mechanisms of actions of hallucinogens, and the results gathered will better our understanding in this area and aid in our insights regarding consciousness and psychotic phenomenon observed in psychotic disorders such as Schizophrenia.
