Effects of serotonergic agonists on firing rates of photically responsive cells in the hamster suprachiasmatic nucleus

Serotonergic neurons from the midbrain raphe nuclei innervate the suprachiasmatic nucleus (SCN) of the hypothalamus, which functions as the dominant pacemaker for mammalian circadian rhythms. We investigated the effects of serotonin (5-HT) on firing rates of light-activated SCN cells in urethane-anesthetized hamsters. Micro-iontophoretic application of 5-HT or 5-HT_1A agonists (8-OH-DPAT and 5-CT) causeda dose-dependent inhibition of spontaneous activity and photic responses in the majority of SCN cells tested. Application of metergoline alone, a non-selective 5-HT antagonist, slightly increased firing rates during darkness and light exposure, suggesting a tonic serotonergic suppression of SCN activity. Metergoline also effectively attenuated suppression induced by the three 5-HT agonists. In addition, the effects of 8-OH-DPAT were blocked by a 5-HT_1A antagonist, SDZ 216-525. However, other putative 5-HT antagonists were weak (propranolol and NAN-190) or ineffective (ketanserin) in blocking the action of 8-OH-DPAT. These results indicate that serotonin has a potent role in reducing photic effects on retinally activated SCN cells in hamsters, and that these effects are mediated by a receptor with properties similar to those of the 5-HT_1A subtype.