Triptans attenuate circadian responses to light

Abstract

Daily exposure to light synchronizes the circadian clock, located in the suprachiasmatic nucleus (SCN), to external day/night cycles. These responses to light can be modified by serotonergic drugs, such as serotonin 5HT1B receptor agonists. Triptans are specific 5HT1B agonists prescribed to treat migraines. Here, we examined the effects of two triptans (zolmitriptan and sumatriptan) on photic phase resetting in Syrian hamsters. Pre-treatment with intra-SCN sumatriptan significantly attenuates, and at higher doses completely blocks, phase advances to light during the late night. Pre-treatment with systemic zolmitriptan significantly attenuates both light-induced phase advances and phase delays. Neither of these drugs, nor their vehicles, causes phase shifts on their own. Pre-treatment with zolmitriptan also significantly reduces the expression of light-induced c-fos in the SCN. Neither zolmitriptan nor vehicle alone induces significant c-fos expression in the SCN. Finally, pre-treatment with zolmitriptan does not attenuate phase shifts to intra-SCN N-methyl-d-aspartate injections, indicating that the mechanism of action for zolmitriptan is likely to be through activation of presynaptic 5HT1B receptors on retinal terminals, thereby decreasing light-induced neurotransmitter release. As triptans are commercially available medications, there is potential for their use in blocking unwanted photic phase shifting during shift-work or jet-lag. Additionally, triptans may also affect the circadian clock in patients receiving them regularly for migraines. Finally, our results may hint at the mechanism by which triptans can alleviate the photophobia that frequently accompanies migraines, namely by activating 5HT1B receptors on retinal terminals elsewhere in the brain, and thereby diminishing visually-evoked neurotransmitter signalling in those areas.

Chronic BMY7378 treatment alters behavioral circadian rhythms

“…5‐HT levels in the SCN are highest during periods of high locomotor activity, most notably during the early night for nocturnal rodents (Dudley et al ., ). In both mice and hamsters, responses to light are generally inhibited by 5‐HT agonists (Glass et al ., ; Rea et al ., ; Pickard et al ., , ; Pickard & Rea, ; Weber et al ., ; Rea & Pickard, ; Antle et al ., ; Smith et al ., ; Basu et al ., ) and are enhanced by 5‐HT antagonists (Moriya et al ., ; Byku & Gannon, ; Gannon, , ; Smart & Biello, ; Takahashi et al ., ; Gannon & Millan, ; Lall & Harrington, ; Kessler et al ., ; Sterniczuk et al ., ; Lungwitz & Gannon, ; Smith et al ., ). Of the various 5‐HT receptor subtypes, the 5‐HT 1A , 5‐HT 1B and 5‐HT 7 receptors seem to be important in modulating photic responses (Rea & Pickard, ; Smith et al ., , ).…”