Hypothalamic dopaminergic neurons in an animal model of seasonal affective disorder

• The number of hypothalamic DA and SST neurons were reduced following light deficiency.
• Blocking orexingergic signaling led to a reduction in the number of hypothalamic DA neurons.
• The number of hypothalamic SST neurons was not affected by orexinergic signaling.
• Light-dependent changes in the hypothalamic DA neurons are likely mediated by orexinergic pathways.

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 12:12 h dim light:dark (DLD) or 8:16 h 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 12:12 h bright light:dark (BLD) condition. Furthermore, we have shown 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.