Attenuated orexinergic signaling underlies depression-like responses induced by daytime light deficiency

Abstract

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.

Hypothalamic dopaminergic neurons in an animal model of seasonal affective disorder

“…Using the diurnal Nile grass rats, we and others have observed depression- and anxiety-like behaviors in winter-like lighting conditions, i.e. short photoperiods [4, 18] or daytime dim lighting [7, 17]. Furthermore, we found that hypothalamic neurons containing the neuropeptide orexin are likely to play a role in mediating the effects of light on mood and anxiety.…”

“…Forced swim test and sweet solution preference test were conducted following the first two daily injections as described in a previous study [7]. Following 5 daily injections of either SB-334867 or vehicle, animals (n = 6/group) were sacrificed between ZT 7–8.…”

“…ICC was carried out as in previous studies [1, 7] using the primary antibodies TH (1:5000, sc-7847, Santa Cruz) or SST (1:10,000, sc-13099, Santa Cruz). Sections were then processed with the avidin-biotin-immunoperoxidase (ABC) technique using DAB as the chromogen.…”

“…Furthermore, we found that hypothalamic neurons containing the neuropeptide orexin are likely to play a role in mediating the effects of light on mood and anxiety. In grass rats, orexin neurons show light-induced activation following acute light exposure [1], and also respond to chronic changes in lighting condition, such that daytime light deficiency leads to a reduction in the number of orexin-expressing neurons [7]. Additionally, treating grass rats housed in summer-like bright light conditions with a selective orexin receptor 1 (OX1R) antagonist induced depression- and anxiety-like behaviors [7].…”

Enhanced inflammatory and T-helper-1 type responses but suppressed lymphocyte proliferation in patients with seasonal affective disorder and treated by light therapy

“…With regards to biological/molecular mechanisms, bright light therapy was reported to increase 5-HT levels in the anterior cingulate and prefrontal cortex by reducing 5-HT transporter binding (Harrison et al, 2014); inhibit orexinergic signaling underlies depression-like responses induced by daytime light deficiency (Deats et al, 2014) and regulate circadian (Lewy et al, 2006).…”