The role of serotonin in photic phase shifting: location of action and molecular underpinnings

Abstract

The serotonergic system modulates the effects of light on the mammalian circadian system. Some serotonergic drugs can greatly enhance the magnitude of the effect light has on shifting the circadian clock. BMY7378, a 5-HT1A mixed agonist/antagonist, enhances photic phase shifts when administered in the late subjective night in hamsters, but not mice. In hamsters, BMY7378 binding directly to receptors in the median raphe nucleus (MRN) appears to be necessary for this effect, but binding in the suprachiasmatic nuclei (SCN) does not appear to be necessary, nor are the serotonergic fibers connecting the MRN directly to the SCN necessary. In order to produce its photic phase shift enhancement effect, BMY7378 alters the activation of some biochemical cascade components, as well as the expression of some genes that are activated or expressed following light exposure in the late subjective night. Buspirone, a 5-HT1A partial agonist, normally attenuates photic phase shifts when administered during the late subjective night, but instead enhances phase shifts in mice lacking the 5-HT1A receptor. The activation of some biochemical cascade components and genes expressed following light exposure are differentially altered following Buspirone administration, depending on whether there was an attenuation or potentiation of photic phase shifts, with or without the 5-HT1A receptors respectively. Together, these results exemplify the complexity of the ability of the serotonergic system to modulate the effects that light stimuli have on the expression of mammalian circadian rhythms.