Seasonal Affective Disorder (SAD) is one of the most common mood disorders with depressive symptoms recurring in winter when there is less sunlight. The fact that light is the most salient factor entraining circadian rhythms leads to the phase-shifting hypothesis, which suggests that the depressive episodes of SAD are caused by misalignments between the circadian rhythms and the habitual sleep times. However, how changes in environmental lighting conditions lead to the fluctuations in mood is largely unknown. The objective of this study is to develop an animal model for some of the features/symptoms of SAD using the diurnal grass rats Arvichantis niloticus and to explore the neural mechanisms underlying the light associated mood changes. Animals were housed in either a 12∶12 hr bright light∶dark (1000lux, BLD) or dim light∶dark (50lux, DLD) condition. The depression-like behaviors were assessed by sweet-taste Saccharin solution preference (SSP) and forced swimming test (FST). Animals in the DLD group showed higher levels of depression-like behaviors compared to those in BLD. The anxiety-like behaviors were assessed in open field and light/dark box test, however no significant differences were observed between the two groups. The involvement of the circadian system on depression-like behaviors was investigated as well. Analysis of locomotor activity revealed no major differences in daily rhythms that could possibly contribute to the depression-like behaviors. To explore the neural substrates associated with the depression-like behaviors, the brain tissues from these animals were analyzed using immunocytochemistry. Attenuated indices of 5-HT signaling were observed in DLD compared to the BLD group. The results lay the groundwork for establishing a novel animal model and a novel experimental paradigm for SAD. The results also provide insights into the neural mechanisms underlying light-dependent mood changes.

Seasonal affective disorder (SAD), a major depressive disorder recurring in the fall and winter, is caused by the reduction of light in the environment, and its depressive symptoms can be alleviated by bright light therapy. Both circadian and monoaminergic systems have been implicated in the etiology of SAD. However, the underlying neural pathways through which light regulates mood are not well understood. The present study utilized a diurnal rodent model, Arvicanthis niloticus, to explore the neural pathways mediating the effects of light on brain regions involved in mood regulation. Animals kept in constant darkness received light exposure in early subjective day, the time when light therapy is usually applied. The time course of neural activity following light exposure was assessed using Fos as a marker in the following brain regions/cells: the suprachiasmatic nucleus (SCN), orexin neurons in the perifornical-lateral hypothalamic area (PF-LHA) and the dorsal raphe nucleus (DRN). A light-induced increase in Fos expression was observed in orexin neurons and the DRN, but not in the SCN. As the DRN is densely innervated by orexinergic inputs, the involvement of orexinergic signaling in mediating the effects of light on the DRN was tested in the second experiment. The animals were injected with the selective orexin receptor type 1 (OXR1) antagonist SB-334867 prior to the light exposure. The treatment of SB-334867 significantly inhibited the Fos induction in the DRN. The results collectively point to the role of orexin neurons in mediating the effects of light on the mood-regulating monoaminergic areas, suggesting an orexinergic pathway that underlies light-dependent mood fluctuation and the beneficial effects of light therapy.

Light has profound effects on mood, as exemplified by seasonal affective disorder (SAD) and the beneficial effects of bright light therapy. However, the underlying neural pathways through which light regulates mood are not well understood. Our previous work has developed the diurnal grass rat, Arvicanthis niloticus, as an animal model of SAD (Leach et al., 2013a, Leach et al., 2013b). By utilizing a 12:12hr Dim Light:Dark (DLD) paradigm that simulates the lower light intensity of winter, we showed that the animals housed in DLD exhibited increased depression-like behaviors in the forced swim test (FST) and sweet solution preference (SSP) compared to animals housed in bright light during the day (BLD). The objective of the present study was to test the hypothesis that light affects mood by acting on the brain orexinergic system in the diurnal grass rat model of SAD. First, orexinA immunoreactivity (OXA-ir) was examined in DLD and BLD grass rats. The results revealed a reduction in the number of OXA-ir neurons in the hypothalamus and attenuated OXA-ir fiber density in the dorsal raphe nucleus of animals in the DLD compared to those in the BLD group. Then, the animals in BLD were treated systemically with SB-334867, a selective orexin 1 receptor (OX1R) antagonist, which led to a depressive phenotype characterized by increased immobility in the FST and a decrease in SSP compared to vehicle-treated controls. The results suggest that attenuated orexinergic signaling is associated with increased depression-like behaviors in grass rats, and support the hypothesis that the orexinergic system mediates the effects of light on mood.

Light has profound effects on mood regulation as exemplified in Seasonal Affective Disorder (SAD) and the therapeutic benefits of light therapy. However, the underlying neural pathways through which light regulates mood are not well understood. Our previous work has developed the diurnal grass rat, Arvicanthis niloticus, as an animal model of SAD. Following housing conditions of either 12:12hr Dim Light:Dark (DLD) or 8:16hr Short Photoperiod (SP), which mimic the lower light intensity or short day-length of winter, respectively, grass rats exhibit an increase in depression-like behavior compared to those housed in a 12:12hr Bright Light:Dark (BLD) condition. Furthermore, we revealed that the orexinergic system is involved in mediating the effects of light on mood and anxiety. To explore other potential neural substrates involved in the depressive phenotype, the present study examined hypothalamic dopaminergic (DA) and somatostatin (SST) neurons in the brains of grass rats housed in DLD, SP and BLD. Using immunostaining for tyrosine hydroxylase (TH) and SST, we found that the number of TH- and SST-ir cells in the hypothalamus was significantly lower in the DLD and SP groups compared to the BLD group. We also found that treating BLD animals with a selective orexin receptor 1 (OX1R) antagonist SB-334867 significantly reduced the number of hypothalamic TH-ir cells. The present study suggests that the hypothalamic DA neurons are sensitive to daytime light deficiency and are regulated by an orexinergic pathway. The results support the hypothesis that the orexinergic pathways mediate the effects of light on other neuronal systems that collectively contribute to light-dependent changes in the affective state.