Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil; Faculdade de Medicina de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Faculdade de Ciências Farmacêuticas de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil; Escola de Enfermagem de Ribeirão Preto, USP, Ribeirão Preto, SP, Brazil.
Behav Brain Res. 2021 Jun 25;408:113295. doi: 10.1016/j.bbr.2021.113295. Epub 2021 Apr 9.
Considering that serotoninergic agents attenuate symptoms of anxiety and are used to treat depression, we investigated whether subchronic treatment with imipramine, a serotonin/noradrenaline reuptake inhibitor, would prevent the anxiogenic-like behaviour induced by acute and/or chronic ethanol withdrawal. We also investigated whether those changes were related to the disfunctioning of hypothalamic-pituitary-adrenal (HPA) axis and serotonergic neurotransmission.
264 Male Wistar rats were treated with ethanol 6% (vol./vol.) for 21 days. Acute ethanol withdrawal was induced by abrupt discontinuation of treatment and sustained for 48 h. Protracted abstinence was sustained for an additional period of 21 days. Behavioural tests included the Elevated Plus Maze (EPM) or Light/Dark Box (LDB) after acute abstinence, and the Forced Swim Test (FST) after protracted abstinence. Imipramine (15 mg/kg, i.p.) was administered 24, 19 and 1 h before EPM or LDB tests.
Acute abstinence decreased exploration of the open arms of the EPM, without changing exploration of LDB. Additionally, chronic abstinent rats displayed more time immobile in the FST, when compared to control animals. These effects were attenuated by imipramine treatment, without changing basal response. Imipramine prevented protracted abstinence -induced decrease in glucocorticoid receptor (GR) and serotonin transporter (SERT) expression in the dorsal hippocampus.
Our findings indicate that chronic ethanol withdrawal affects the hippocampal serotonergic system by decreasing serotonin transporter expression. It also disturbs the HPA axis functioning through an imbalance on GR and mineralocorticoid (MR) expression.
鉴于 5-羟色胺能药物可减轻焦虑症状，并用于治疗抑郁症，我们研究了 5-羟色胺/去甲肾上腺素再摄取抑制剂丙咪嗪的亚慢性治疗是否会预防急性和/或慢性乙醇戒断引起的焦虑样行为。我们还研究了这些变化是否与下丘脑-垂体-肾上腺 (HPA) 轴和 5-羟色胺能神经传递功能障碍有关。
264 只雄性 Wistar 大鼠用 6%（体积/体积）乙醇处理 21 天。急性乙醇戒断通过突然停止治疗持续 48 小时诱导。长期戒断再持续 21 天。行为测试包括急性戒断后高架十字迷宫（EPM）或明暗箱（LDB），以及长期戒断后强迫游泳测试（FST）。丙咪嗪（15mg/kg，ip）在 EPM 或 LDB 测试前 24、19 和 1 小时给药。
急性戒断减少了 EPM 开放臂的探索，而不改变 LDB 的探索。此外，与对照动物相比，慢性戒断大鼠在 FST 中静止不动的时间更多。这些作用通过丙咪嗪治疗得到减轻，而不改变基础反应。丙咪嗪可预防慢性乙醇戒断引起的背海马糖皮质激素受体 (GR) 和 5-羟色胺转运体 (SERT) 表达减少。
我们的发现表明，慢性乙醇戒断通过降低 5-羟色胺转运体的表达来影响海马 5-羟色胺能系统。它还通过 GR 和盐皮质激素（MR）表达失衡扰乱 HPA 轴功能。
