LSD and Serotonin Receptor Function

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DESCRIPTION(Provided by applicant): Schizophrenia is a psychiatric disorder with core symptoms that include delusions, disorganized thought and speech, and hallucinations. The neural substrate for the formation of hallucinations is, at present, unclear. In this application, biochemical and behavioral experiments will be performed to examine the loci of action of the hallucinogenic drug lysergic acid diethylamide (LSD). LSD is thought to mediate its actions primarily through serotonin-2A (5-HT2a) and serotonin-2C (5-HT2c) receptors. Specific Aim I will examine the contribution of 5-HT2A and 5-HT2c receptors to the induction of the immediate early gene, c-fos, in rat brain after LSD treatment. Specific Aim H will utilize direct microinfusion to isolate which brain site(s) are involve in the LSD-induced discriminative stimulus. Finally, Specific Aim Ill will examine whether there are functional alterations of 5-HT2A and 5-HT2c receptors after repeated LSD exposure. A long-term goal is to understand the neuronal mechanism of action of LSD, a potent hallucinogen, and how these neuronal processes might be dysfunctional in a disease state such as schizophrenia.