Departamento de Psicobiología y Metodología en Ciencias del Comportamiento, Facultad de Psicología, Universidad Complutense de Madrid, 28224 Spain.
Laboratorio de Medicina Regenerativa, Instituto de Investigación Biomédica de Málaga (IBIMA), UGC Salud Mental, Hospital Regional Universitario de Málaga, Av. Carlos Haya 82, sótano, Málaga 29010, Spain.
Eur Neuropsychopharmacol. 2019 Jun;29(6):756-765. doi: 10.1016/j.euroneuro.2019.03.012. Epub 2019 May 4.
the role that antidepressants play on alcohol consumption is not well understood. Previous studies have reported that treatment with a Selective Serotonin Reuptake Inhibitor (SSRIs) increases alcohol consumption in an animal model of relapse, however it is unknown whether this effect holds for other antidepressants such as the atypical dopamine/norepinephrine reuptake inhibitors (SNDRI).
the main goal of the present study was to compare the effects of two classes of antidepressants drugs, bupropion (SNDRI) and fluoxetine (SSRI), on alcohol consumption during relapse. Since glutamatergic and endocannabinoid signaling systems plays an important role in alcohol abuse and relapse, we also evaluated the effects of both antidepressants onthe expression of the main important genes and proteins of both systems in the prefrontal cortex, a critical brain region in alcohol relapse.
rats were trained to self-administered alcohol. During abstinence, rats received a 14d-treatment with vehicle, fluoxetine (10 mg/kg) or bupropion (20 mg/kg), and we evaluated alcohol consumption during relapse for 3 weeks. Samples of prefrontal cortex were taken to evaluate the mRNA and protein expression of the different components of glutamatergic and endocannabinoid signaling systems.
fluoxetine treatment induced a long-lasting increase in alcohol consumption during relapse, an effect that was not observed in the case of bupropion treatment. The observed increases in alcohol consumption were accompanied by distinct alterations in the glutamate and endocannabinoid systems.
our results suggest that SSRIs can negatively impact alcohol consumption in relapse while SNDRIs have no effects. The observed increase in alcohol consumption are accompanied by functional alterations in the glutamatergic and endocannabinoid systems. This finding could open new strategies for the treatment of depression in patients with alcohol use disorders.
抗抑郁药在酒精消费中的作用尚不清楚。先前的研究报告称，在复发的动物模型中，使用选择性 5-羟色胺再摄取抑制剂 (SSRIs) 治疗会增加酒精消费，但尚不清楚这种效应是否适用于其他抗抑郁药，如非典型多巴胺/去甲肾上腺素再摄取抑制剂 (SNDRI)。
本研究的主要目的是比较两类抗抑郁药，安非他酮 (SNDRI) 和氟西汀 (SSRIs)，在复发期间对酒精消费的影响。由于谷氨酸能和内源性大麻素信号系统在酒精滥用和复发中起着重要作用，我们还评估了这两种抗抑郁药对前额叶皮层中这两个系统的主要重要基因和蛋白表达的影响，前额叶皮层是酒精复发的关键脑区。
大鼠接受酒精自我给药训练。在禁欲期间，大鼠接受了为期 14 天的载体、氟西汀 (10mg/kg) 或安非他酮 (20mg/kg) 治疗，我们评估了 3 周的复发期间的酒精消费。取前额叶皮层样本，评估谷氨酸能和内源性大麻素信号系统的不同成分的 mRNA 和蛋白表达。
氟西汀治疗在复发期间诱导了长时间的酒精消费增加，而安非他酮治疗则没有观察到这种效果。观察到的酒精消费增加伴随着谷氨酸和内源性大麻素系统的明显改变。
我们的结果表明，SSRIs 可能会对复发期间的酒精消费产生负面影响，而 SNDRIs 则没有影响。观察到的酒精消费增加伴随着谷氨酸能和内源性大麻素系统的功能改变。这一发现为治疗患有酒精使用障碍的抑郁症患者提供了新的策略。
