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-HT 1 B ) receptors on retinal terminals in the SCN inhibits retinohypothalamic neurotransmission and light-induced behavioral phase shifts. To assess the role of 5-HT 1 B receptors in photic entrainment, 5-HT 1 B receptor knockout (5-HT 1 B 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-HT 1 B KO animals did not. 5-HT 1 B 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-HT 1 B 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-HT 1 B 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-HT 1 B 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-HT 1 B KO mouse may be useful for investigating the altered entrainment evident during this serious mood disorder.