A NOVEL ADENYLYL CYCLASE-ACTIVATING SEROTONIN RECEPTOR (5-HT7) IMPLICATED IN THE REGULATION OF MAMMALIAN CIRCADIAN-RHYTHMS

We report the cloning and characterization of a novel serotonin recept or, designated as 5-HT7, which is coupled to the stimulation of adenyl yl cyclase. 5-HT7 mRNA is expressed discretely throughout the CNS, pre dominantly in the thalamus and hypothalamus. 5-HT7 has a unique pharma cological profile that redefines agonist and antagonist classification of ligands previously thought to be ''selective.'' The circadian phas e of spontaneous neuronal activity of the rat suprachiasmatic nucleus of the hypothalamus advances in response to serotonin ligands with a p harmacological profile consistent exclusively with that of 5-HT7. Thes e findings suggest a physiological role in the regulation of circadian rhythms for one subtype of serotonin receptor, 5-HT7, and provide a p harmacological test to evaluate its role in other neuronal systems.