The darkness and the light: diurnal rodent models for seasonal affective disorder

Abstract

The development of animal models is a critical step for exploring the underlying pathophysiological mechanisms of major affective disorders and for evaluating potential therapeutic approaches. Although most neuropsychiatric research is performed on nocturnal rodents, differences in how diurnal and nocturnal animals respond to changing photoperiods, combined with a possible link between circadian rhythm disruption and affective disorders, has led to a call for the development of diurnal animal models. The need for diurnal models is most clear for seasonal affective disorder (SAD), a widespread recurrent depressive disorder that is linked to exposure to short photoperiods. Here, we briefly review what is known regarding the etiology of SAD and then examine progress in developing appropriate diurnal rodent models. Although circadian disruption is often invoked as a key contributor to SAD, a mechanistic understanding of how misalignment between endogenous circadian physiology and daily environmental rhythms affects mood is lacking. Diurnal rodents show promise as models of SAD, as changes in affective-like behaviors are induced in response to short photoperiods or dim-light conditions, and symptoms can be ameliorated by brief exposure to intervals of bright light coincident with activity onset. One exciting avenue of research involves the orexinergic system, which regulates functions that are disturbed in SAD, including sleep cycles, the reward system, feeding behavior, monoaminergic neurotransmission and hippocampal neurogenesis. However, although diurnal models make intuitive sense for the study of SAD and are more likely to mimic circadian disruption, their utility is currently hampered by a lack of genomic resources needed for the molecular interrogation of potential mechanisms.

Circadian rhythms-related disorders in diurnal fat sand rats under modern lifestyle conditions: A review

“…Such a response to laboratory conditions acclimation has not been documented in nocturnal rodents ( Weber and Hohn, 2005 ; Barak and Kronfeld-Schor, 2013 ; Shankar and Williams, 2021 ). We hypothesize that this observed reduction in the robustness of the circadian system of diurnal species increases their susceptibility to circadian rhythm-related disturbances and disorders.…”

Light-induced synchronization of the SCN coupled oscillators and implications for entraining the HPA axis

“…Seasonal changes can cause misalignment of the physiological systems. For instance, seasonal affective disorder (SAD) is characterized by a cyclical pattern of depression that occurs during short photoperiods and then fades during longer photoperiods ( 81 , 82 ). Different individuals react differently to seasonal changes and can develop differential severity and symptoms of SAD.…”