Effects of antidepressants on 5-HT7 receptor regulation in the rat hypothalamus

Recent evidence suggests that a novel serotonin receptor 5-HT7 localized in the hypothalamus downregulates in response to treatment with the antidepre ssant fluoxetine (Sleight et al. 1995). This receptor has also been implica ted in the regulation of circadian rhythms (Lovenberg et al. 1993). Here, w e show that several agents administered in a profile consistent with activi ty at the 5-HT7 receptor produce significant functional Fos immunoreactivit y in the suprachiasmatic nucleus (SCN), an effect reduced upon chronic expo sure. Furthermore, binding studies demonstrate that chronic administration of Fos-inducing agents produces a neuroadaptive downregulation of the 5-HT7 receptor in the hypothalamus. The current studies extend the previous obse rvations to include several pharmacologically distinct antidepressants. In addition, these studies provide further evidence to support the role of the 5-HT7 receptor in the mechanism of anti-depressant action and in the regul ation of circadian rhythms controlled by the SCN. (C) 1999 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.