The goal of the project is to localize and characterize the serotonin-1 (5-HT1) subtypes in three regions of the rat brain: the hippocampus, the striatum and the hypothalamus. We will utilize in vitro receptor binding studies to characterize three serotonin-1 subtypes, 5-HT1A, 5-HT1B and 5-HT1C. These serotonin binding sites will be identified and quantified by direct ligand binding assays using (3H)-8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT), lodo-cyanopindolol (125I-CYP) and (3H)-mesulergine as the probes for 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. We will compare subtype differences and similarities in their pharmacological response to various classes of drugs. Detailed competition experiments will be used to separate the component of ligand binding. Some initial studies in our laboratory have demonstrated the existence of the 5-HT1A and 5-HT1B recognition sites in the hippocampus. Such work is now in progress with the 5-HT1C subtype. With various neuronal lesions we will gain information on the cellular localization of these serotonin sites (pre- or post-synaptic terminals or serotonin neurons). Finally, we will determine the functional linked to these sties, namely the adenylate cyclase or the phosphoinositol hydrolysis system. Studies of the features of the serotonin-1 binding sites (5-HT1A, 5-HT1B and 5-HT1C), the relationship between these sites and central serotonin mediated effects will help elucidate the role of these serotonin binding sites in the mechanism of serotonergic drug action and in the pathophysiology of some disease states.
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