Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
Department of Psychiatry and Mental Health and MRC Unit on Anxiety & Stress Disorders, Faculty of Health Sciences, University of Cape Town, Cape Town, 7925, South Africa.
Metab Brain Dis. 2018 Apr;33(2):433-441. doi: 10.1007/s11011-017-0123-0. Epub 2017 Oct 16.
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.
母体分离(MS)是一种成熟的抑郁症啮齿动物模型。在青春期给予慢性持续光照(CCL)治疗已被证明可以逆转 MS 引起的类似抑郁的行为。我们旨在通过研究多巴胺能、5-羟色胺能和食欲素能系统的参与,进一步阐述光照的抗抑郁作用。使用 MS 诱导成年雄性 Sprague-Dawley 大鼠发生变化,其中一些大鼠在青春期也接受了 3 周的 CCL 治疗。在 P80,大鼠断头取脑,采用体外灌流技术分析伏隔核(NAc)中谷氨酸和钾刺激的多巴胺释放。酶联免疫吸附试验用于测量下丘脑和前额叶皮质(PFC)中的 5-羟色胺(5-HT)水平。Western blot 用于测量 PFC 中的食欲素受体 1(OXR-1)和 2(OXR-2)。MS 并未影响这些大鼠的 5-HT 水平。然而,CCL 增加了下丘脑 5-HT 并降低了 PFC 中的 5-HT 水平。CCL 对 MS 分离和非分离大鼠 PFC 中的 OXR 水平产生相反的影响。MS 增加了 PFC 中的 OXR-1 和 OXR-2 水平,CCL 治疗使这种增加正常化。MS 降低了 NAc 中的谷氨酸刺激的多巴胺释放,CCL 没有逆转这种作用。本研究结果表明,CCL 治疗影响 MS 模型中的 5-HT 和食欲素能系统,而不影响 MS 引起的 NAc 中多巴胺释放减少。食欲素能系统的变化逆转可能与 CCL 在抑郁症中的抗抑郁作用特别相关。