8-OH-DPAT as a 5-HT7 agonist: phase shifts of the circadian biological clock through increases in cAMP production

摘要: Neurons in the suprachiasmatic nucleus (SCN), site of endogenous biological clock mammals, fire spontaneously, peaking firing rate near ZT6 or at midpoint light phase a 12:12 light-dark cycle. In rat hypothalamic slices, tissue incubations with drugs can produce shift this daily rhythm, magnitude which is dependent upon dose and time treatment. Previous work 8-OH-DPAT had noted its ability to advance, an earlier occurrence peak neuronal firing, when applied ZT6. Activation 5-HT7 receptors was thought be responsible for shift, despite clear preference 5-HT1A sites terms receptor binding affinity. present work, actions SCN slices were confirmed expanded include additional dose-response antagonist treatments. By itself, produced concentration-dependent advance that sensitive co-application antagonists (ritanserin, mesulergine, SB-269970), but not (WAY-100,635, UH-301). Assignment mechanisms employed accomplished experiments measuring affinities generation cAMP, latter monitored HEK-293 cell line expressing r5-HT7 derived from SCN. The results indicate increases observed cAMP levels are small appear sufficient pharmacological resetting pacemaker. aiding identification 5-HT subtype shifts changes, represents important tool activation, essentially broadening role as prototypical agonist one combining these two activities.