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

Abstract Recent evidence suggests that a novel serotonin receptor 5-HT 7 localized in the hypothalamus downregulates in response to treatment with the antidepressant fluoxetine (Sleight et al. 1995) . This receptor has also been implicated in the regulation of circadian rhythms (Lovenberg et al. 1993) . Here, we show that several agents administered in a profile consistent with activity at the 5-HT 7 receptor produce significant functional Fos immunoreactivity in the suprachiasmatic nucleus (SCN), an effect reduced upon chronic exposure. Furthermore, binding studies demonstrate that chronic administration of Fos-inducing agents produces a neuroadaptive downregulation of the 5-HT 7 receptor in the hypothalamus. The current studies extend the previous observations to include several pharmacologically distinct antidepressants. In addition, these studies provide further evidence to support the role of the 5-HT 7 receptor in the mechanism of antidepressant action and in the regulation of circadian rhythms controlled by the SCN.