Abstract
Seasonal affective disorder (SAD), beyond mood changes, is characterized by alterations in daily rhythms of behavior and physiology. The pathophysiological conditions of SAD involve changes in day length and its first-line treatment is bright light therapy. Animal models using nocturnal rodents have been studied to elucidate the neurobiological mechanisms of depression, but might be ill suited to study the therapeutic effects of light in SAD since they exhibit light-aversive responses. Here Arvicanthis ansorgei, a diurnal rodent, was used to determine behavioral, molecular and brain dopamine changes in response to exposure to a winter-like photoperiod consisting of a light–dark cycle with 8 h of light, under diminished light intensity, and 16 h of darkness. Furthermore, we evaluated whether timed-daily bright light exposure has an effect on behavior and brain physiology of winter-like exposed animals. Arvicanthis under a winter-like condition showed alterations in the synchronization of the locomotor activity rhythm to the light–dark cycle. Moreover, alterations in day–night activity of dopaminergic neurotransmission were revealed in the nucleus accumbens and the dorsal striatum, and in the day–night clock gene expression in the suprachiasmatic nucleus. Interestingly, whereas dopamine disturbances were reversed in animals exposed to daily light at early or late day, altered phase of the daily rhythm of locomotion was reverted only in animals exposed to light at the late day. Moreover, Per2 gene expression in the SCN was also affected by light exposure at late day in winter-like exposed animals. These findings suggest that light induces effects on behavior by mechanisms that rely on both circadian and rhythm-independent pathways influencing the dopaminergic circuitry. This last point might be crucial for understanding the mechanisms of non-pharmacological treatment in SAD.
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Acknowledgements
We thank Dr. Dominique Ciocca for help with Arvicanthis breeding. Funding sources of the present study were provided by the Agence National de la Recherche (ANR-14-CE13-0002-01 ADDiCLOCK JCJC to JM), the Centre National de la Recherche Scientifique (JM), and the Institut Danone France-Fondation pour la Recherche Médicale Consortium (JM). JI is a Ph.D. NeuroTime program fellow, an Erasmus Mundus program funded by the European Commission (NeuroTime Grant: 520124-1-2011-1-FR-ERA). Riboprobe used for Per2 gene detection was generously provided by Prof. Hitoshi Okamura (Kyoto University, Japan). We thank Dr. Hughes Dardente (University of Tours, France) for the Avp and Bmal1 clones.
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Itzhacki, J., Clesse, D., Goumon, Y. et al. Light rescues circadian behavior and brain dopamine abnormalities in diurnal rodents exposed to a winter-like photoperiod. Brain Struct Funct 223, 2641–2652 (2018). https://doi.org/10.1007/s00429-018-1655-8
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DOI: https://doi.org/10.1007/s00429-018-1655-8