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
- 180 Downloads
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.
KeywordsDepression Maternal separation Chronic constant light Dopamine, serotonin Orexin
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.
- Bogen S, Legenbauer T, Gest S, Holtmann M (2016) Morning bright light therapy: a helpful tool for reducing comorbid symptoms of affective and behavioral dysregulation in juvenile depressed inpatients? A pilot trail. Z Kinder Jugendpsychiatr Psychother 44:1–8Google Scholar
- Bowrey HE, James MH, Aston-Jones G (2017) New directions for the treatment of depression: targeting the photic regulation of arousal and mood (PRAM) pathway. Depress Anxiety. https://doi.org/10.1002/da.22635 [Epub ahead of print]
- Brenes JC, Rodríguez O, Fornaguera J (2008) Differential effect of environment enrichment and social isolation on depressive-like behavior, spontaneous activity and serotonin and norepinephrine concentration in prefrontal cortex and ventral striatum. Pharmacol Biochem Behav 89:85–93CrossRefPubMedGoogle Scholar
- Honma K, Hiroshige T (1978) Endogenous ultradian rhythms in rats exposed to prolonged continuous light. Am J Phys 4:R250–R256Google Scholar
- Kim T-K, Kim J-E, Park J-Y, Lee J-E, Choi J, Kim H, Lee E-H, Kim S-W, Lee J-K, Kang H-S, Han P-L (2015) Antidepressant effects of exercise are produced via suppression of hypocretin/orexin and melanin-concentrating hormone in the basolateral amygdala. Neurobiol Dis 79:59–69CrossRefPubMedGoogle Scholar
- de Lecea L, Kilduff TS, Peyron C, Gao XB, Foye PE, Danielson PE, Fukuhara C, Battenberg EL, Gautvik VT, Bartlett FS, Frankel VW, van den Pol AN, Bloom FE, Gautvik KM, Sutcliff JG (1998) The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A 95:322–327CrossRefPubMedPubMedCentralGoogle Scholar
- SABS Standards Division (2008) South African national standard. The care and use of animals for scientific purposes. SANS 10386:2008. SABS Standards Division, PretoriaGoogle Scholar
- Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson S, Arch JRS, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behaviour. Cell 92:573–585CrossRefPubMedGoogle Scholar