5-HT1B Receptor Knockout Mice Exhibit an Enhanced Response to Constant Light

Abstract

Serotonin (5-HT) can act presynaptically at 5-HT_1B receptors on retinal terminals in the suprachiasmatic nucleus (SCN) to inhibit glutamate release, thereby modulating the effects of light on circadian behavior. 5-HT_1B receptor agonists (1) inhibit light-inducedphase shifts of circadian activity rhythms, (2) attenuate light-induced Fos expression in the SCN, and (3) reduce the amplitude of optic nerve–evoked excitatory postsynaptic currents in SCN neurons in vitro. To determine whether functional disruption of the 5-HT_1B presynaptic receptors would result in an amplified response of the SCN to light, the period ([.tau]) of the circadian rhythm of wheel-running activity was estimated under several different conditions in 5-HT_1B receptor knockout (KO) mice and genetically matched wild- typeanimals. Under constant light (LL) conditions, the [.tau] of 5-HT_1B receptor KO mice was significantly greater than the [.tau] of wild-type mice. Aquantitative analysis of the wheel-running activity revealed no differences between wild-type and KO mice in either total activity or the temporal distribution of activity under LL conditions, suggesting that the observed increase in [.tau] was not a function of reduced activity. Under constant dark conditions, the period of the circadian rhythm of wheel-running activity of wild-type and 5-HT_1B receptor KO mice was similar. In addition, no differences were noted between wild-type and 5-HT_1Breceptor KO mice in the rate of reentrainment toa6h phase advance in the 12:12 light:dark cycle or in phase shifts in response to a 10 min light pulse presented at circadian time 16. The enhanced response of the SCN circadian clock of the 5- HT_1B receptor KO mice to LLconditions is consistent with the hypothesis that the endogenous activation of 5-HT_1B presynaptic receptors modulates circadian behavior by attenuating photic input to the SCN.