Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Int J Neuropsychopharmacol. 2011 Mar;14(2):201-10. doi: 10.1017/S1461145710000489. Epub 2010 May 19.
Increasing attention is now focused on reduced dopaminergic neurotransmission in the forebrain as participating in depression. The present paper assessed whether effective antidepressant (AD) treatments might counteract, or compensate for, such a change by altering the neuronal activity of dopaminergic neurons in the ventral tegmental area (VTA-DA neurons), the cell bodies of the mesocorticolimbic dopaminergic system. Eight AD drugs or vehicle were administered to rats for 14 d via subcutaneously implanted minipumps, at which time single-unit electrophysiological activity of VTA-DA neurons was recorded under anaesthesia. Further, animals received a series of five electroconvulsive shocks (ECS) or control procedures, after which VTA-DA activity was measured either 3 d or 5 d after the last ECS. Results showed that the chronic administration of all AD drugs tested except for the monoamine oxidase inhibitor increased the spontaneous firing rate of VTA-DA neurons, while effects on 'burst' firing activity were found to be considerably less notable or consistent. ECS increased both spontaneous firing rate and burst firing of VTA-DA neurons. It is suggested that the effects observed are consistent with reports of increased dopamine release in regions to which VTA neurons project after effective AD treatment. However, it is further suggested that changes in VTA-DA neuronal activity in response to AD treatment should be most appropriately assessed under conditions associated with depression, such as stressful conditions.
现在越来越多的人关注到前脑内多巴胺能神经传递的减少与抑郁症有关。本文评估了有效的抗抑郁(AD)治疗是否可以通过改变腹侧被盖区(VTA-DA 神经元)的多巴胺能神经元的神经元活动来对抗或补偿这种变化,VTA-DA 神经元是中皮质边缘多巴胺能系统的细胞体。通过皮下植入的微型泵向大鼠连续 14 天给予 8 种 AD 药物或载体,此时在麻醉下记录 VTA-DA 神经元的单细胞电生理活性。进一步的,动物接受一系列五次电惊厥(ECS)或对照程序,在最后一次 ECS 后 3 天或 5 天测量 VTA-DA 活性。结果表明,除单胺氧化酶抑制剂外,所有测试的 AD 药物的慢性给药均增加了 VTA-DA 神经元的自发放电率,而对“爆发”放电活动的影响则不太显著或不一致。ECS 增加了 VTA-DA 神经元的自发放电率和爆发放电率。这表明,观察到的效果与有效的 AD 治疗后 VTA 神经元投射区域多巴胺释放增加的报道一致。然而,进一步的,建议在与抑郁相关的条件下,如应激条件下,评估 AD 治疗后 VTA-DA 神经元活动的变化。