Demontis Francesca, Serra Francesca, Serra Gino
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.
Department of General Psychology, University of Padua, Italy.
Curr Neuropharmacol. 2017 Apr;15(3):417-423. doi: 10.2174/1570159X14666160715165648.
Mania seems to be associated with an increased dopamine (DA) transmission. Antidepressant treatments can induce mania in humans and potentiated DA transmission in animals, by sensitizing DA D2 receptors in the mesolimbic system. We have suggested that the sensitization of D2 receptors may be responsible of antidepressant-induced mania. This review aims to report the experimental evidence that led to the hypothesis that antidepressant-induced DA receptors dysregulation can be considered an animal model of bipolar disorder.
We reviewed papers reporting preclinical and clinical studies on the role of DA in the mechanism of action of antidepressant treatments and in the patho-physiology of mood disorders.
A number of preclinical and clinical evidence suggests that mania could be associated with an increased DA activity, while a reduced function of this neurotransmission might underlie depression. Chronic treatment with imipramine induces a sensitization of DA D2 receptors in the mesolimbic system, followed, after drug discontinuation, by a reduced sensitivity associated with an increased immobility time in forced swimming test of depression (FST). Blockade of glutamate NMDA receptors by memantine administration prevents the imipramine effect on DA receptors sensitivity and on the FST.
We suggest that chronic treatment with antidepressants induces a behavioural syndrome that mimics mania (the sensitization of DA receptors), followed by depression (desensitization of DA receptors and increased immobility time in the FST), i.e. an animal model of bipolar disorder. Moreover the observation that memantine prevents the "bipolar-like" behavior, suggests that the drug may have an antimanic and mood stabilizing effect. Preliminary clinical observations support this hypothesis.
躁狂似乎与多巴胺（DA）传递增加有关。抗抑郁治疗可在人类中诱发躁狂，并通过使中脑边缘系统中的DA D2受体敏感化，在动物中增强DA传递。我们曾提出，D2受体的敏感化可能是抗抑郁药诱发躁狂的原因。本综述旨在报告实验证据，这些证据导致了这样一种假说，即抗抑郁药诱发的DA受体失调可被视为双相情感障碍的动物模型。
我们回顾了报告DA在抗抑郁治疗作用机制及心境障碍病理生理学中作用的临床前和临床研究论文。
大量临床前和临床证据表明，躁狂可能与DA活性增加有关，而这种神经传递功能降低可能是抑郁症的基础。丙咪嗪的慢性治疗会导致中脑边缘系统中DA D2受体的敏感化，停药后，会出现敏感性降低，并伴有抑郁强迫游泳试验（FST）中不动时间增加。美金刚给药阻断谷氨酸NMDA受体可防止丙咪嗪对DA受体敏感性和FST的影响。
我们认为，抗抑郁药的慢性治疗会诱发一种模仿躁狂的行为综合征（DA受体的敏感化），随后是抑郁（DA受体的脱敏和FST中不动时间增加），即双相情感障碍的动物模型。此外，美金刚可预防“双相样”行为这一观察结果表明，该药物可能具有抗躁狂和情绪稳定作用。初步临床观察支持这一假说。
