Antidepressant-like effect of bright light is potentiated by L-serine administration in a mouse model of seasonal affective disorder.
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.
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Misato
M
Kawai
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Ryosei
R
Goda
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Tsuyoshi
T
Otsuka
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Ayaka
A
Iwamoto
Research Institute, FANCL Co., Yokohama 244-0806, Japan.
Nobuo
N
Uotsu
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan.
Mitsuhiro
M
Furuse
Laboratory of Regulation in Metabolism and Behavior, Faculty of Agriculture, Kyushu University, Fukuoka 812-8581, Japan. Electronic address: syasuo@brs.kyushu-u.ac.jp.
Shinobu
S
Yasuo
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000494:pharmacology; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010789:Phototherapy / Q000379:methods*; D011897:Random Allocation; D016574:Seasonal Affective Disorder / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D012694:Serine / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology
D000928:Antidepressive Agents; D005473:Fluoxetine; D012694:Serine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors
Depression-like behavior; Mouse; Raphe nuclei; Seasonal affective disorder; Serotonin; c-Fos