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Chronic light exposure alters serotonergic and orexinergic systems in the rat brain and reverses maternal separation-induced increase in orexin receptors in the prefrontal cortex

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Abstract

Maternal separation (MS) is a well-established rodent model of depression. Chronic constant light (CCL) treatment during adolescence has been shown to reverse the depression-like behaviour induced by MS. We aimed to further delineate the antidepressant effect of light by investigating the involvement of the dopaminergic, serotonergic and orexinergic systems. MS was used to induce changes in adult male Sprague-Dawley rats, some of whom were also treated with CCL for 3 weeks during adolescence. At P80, rats were decapitated and brain tissue collected for analysis of glutamate- and potassium-stimulated dopamine release in the nucleus accumbens (NAc) using an in vitro superfusion technique. Enzyme-linked immunosorbent assays were employed to measure 5-hydroxytryptamine (5-HT) levels in the hypothalamus and prefrontal cortex (PFC). Western blotting was used to measure orexin receptor 1 (OXR-1) and 2 (OXR-2) in the PFC. MS did not affect 5-HT levels in these rats. However, CCL increased hypothalamic 5-HT and reduced 5-HT levels in the PFC. CCL had opposite effects on OXR levels in the PFC of maternally separated and non-separated rats. MS increased OXR-1 and OXR-2 levels in the PFC, an effect that was normalized by CCL treatment. MS reduced glutamate-stimulated dopamine release in the NAc, an effect that was not reversed by CCL. The present results suggest that CCL treatment affects 5-HT and orexinergic systems in the MS model while not affecting the MS-induced decrease in dopamine release in the NAc. The reversal of changes in the orexinergic system may be of particular relevance to the antidepressant effect of CCL in depression.

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Acknowledgements

The authors would like to thank the National Research Foundation (NRF) for financial support. DJS is supported by the South African MRC. Any opinion, findings and conclusions, or recommendations expressed in this material are those of the authors and therefore the NRF does not accept any liability in regard thereto. We would also like to thank Ms. Nuraan Ismail for the care of the animals.

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Dimatelis, J.J., Mtintsilana, A., Naidoo, V. et al. Chronic light exposure alters serotonergic and orexinergic systems in the rat brain and reverses maternal separation-induced increase in orexin receptors in the prefrontal cortex. Metab Brain Dis 33, 433–441 (2018). https://doi.org/10.1007/s11011-017-0123-0

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