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Background: Bright light therapy (BLT) is the first-line treatment for seasonal affective disorder. However, the
neural mechanisms underlying BLT are unclear. To begin filling this gap, the present study examined the impact
of BLT on sleep/wakefulness, daily rhythms, and the wakefulness-promoting orexin/hypocretin system in a
diurnal rodent, Nile grass rats (Arvicanthis niloticus).
Methods: Male and female grass rats were housed under a 12:12 h light/dark cycle with dim light (50 lx) during
the day. The experimental group received daily 1-h early morning BLT (full-spectrum white light, 10,000 lx),
while the control group received narrowband red light for 4 weeks. Sleep/wakefulness and in-cage locomotor
activity were monitored, followed by examination of hypothalamic prepro-orexin and orexin receptors OX1R and
OX2R expression in corticolimbic brain regions.
Results: The BLT group had higher wakefulness during light treatment, better nighttime sleep quality, and
improved daily rhythm entrainment compared to controls. The impact of BLT on the orexin system was sex- and
brain region-specific, with males showing higher OX1R and OX2R in the CA1, while females showed higher
prepro-orexin but lower OX1R and OX2R in the BLA, compared to same-sex controls.
Limitations: The present study focused on the orexin system in a limited number of brain regions at a single time
point. Sex wasn't a statistical factor, as male and female cohorts were run independently.
Conclusions: The diurnal grass rats show similar behavioral responses to BLT as humans, thus could be a good
model for further elucidating the neural mechanisms underlying the therapeutic effects of BLT.