Research reportAntidepressant-like effect of bright light is potentiated by l-serine administration in a mouse model of seasonal affective disorder

•Bright light reduced depression-like behavior in mice exposed to short-day condition.•Effect of light on depression-like behavior was potentiated by l-serine injection.•Serotonin signals in the raphe nuclei were enhanced by bright light and l-serine.•Bright light may elicit an antidepressant-like effect via enhanced serotonin signals.

Bright light therapy is used as the primary treatment for seasonal affective disorder; however, the mechanisms underlying its antidepressant effect are not fully understood. Previously, we found that C57BL/6J mice exhibit increased depression-like behavior during a short-day condition (SD) and have lowered brain serotonin (5-HT) content. This study analyzed the effect of bright light on depression-like behaviors and the brain serotonergic system using the C57BL/6J mice. In the mice maintained under SD, bright light treatment (1000 lx, daily 1 h exposure) for 1 week reduced immobility time in the forced swimming test and increased intake of saccharin solution in a saccharin intake test. However, the light treatment did not modify 5-HT content and selective 5-HT uptake in the amygdala, or temporal patterns of core body temperature and wheel-running activity throughout a day. In the next experiment, we attempted to enhance the effect of bright light by using l-serine, a precursor of d-serine that acts as an N-methyl-d-aspartic acid receptor coagonist. Daily subcutaneous injection of l-serine for 2 weeks prior to the bright light strongly reduced the immobility time in the forced swimming test, suggesting a synergistic effect of light and l-serine. Furthermore, bright light increased the total number of 5-HT-immunoreactive cells and cells that had colocalized 5-HT and c-Fos immunosignals in several subregions of the raphe nuclei. These effects were potentiated by prior injection of l-serine. These data suggest that the bright light may elicit an antidepressant-like effect via enhanced 5-HT signals in the brain and l-serine can enhance these effects.