Photic entrainment is altered in the 5-HT1B receptor knockout mouse

The hypothalamic suprachiasmatic nucleus (SCN) is a circadian oscillator that receives glutamatergic afferents from the retina and serotonergic afferents from the midbrain. Activation of presynaptic serotonin 1B (5-HT1B) receptors on retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and light-induced behavioral phase shifts. To assess the role of 5-HT1B receptors in photic entrainment, 5-HT1B receptor knockout (5-HT1B KO) and wild-type (WT) mice were maintained in non-24 h L:D cycles (T cycles). WT mice entrained to T = 21 h and T = 22 h cycles, whereas 5-HT1B KO animals did not. 5-HT1B KO animals did entrain to T = 23 h and T = 26 h cycles, although their phase angle of entrainment was altered compared to WT animals. 5-HT1B KO mice were significantly more phase delayed under T = 23 h conditions and significantly more phase advanced under T = 26 h conditions compared to WT mice. When 5-HT1B KO mice were housed in a T = 23 h short-day photoperiod (9.5L:13.5D), the delayed phase angle of entrainment was more pronounced. Light-induced phase shifts were reduced in 5-HT1B KO mice, consistent with their behavior in T cycles, suggesting an attenuated response to light. Based on previous work, this attenuated response to light might not have been predicted but can be explained by consideration of GABAergic mechanisms within the SCN. Phase-delayed circadian rhythms during the short days of winter are characteristic of patients suffering from seasonal affective disorder, and 5-HT has been implicated in its pathophysiology. The 5-HT1B KO mouse may be useful for investigating the altered entrainment evident during this serious mood disorder.