Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de Valencia, 46100 Burjassot, Spain.
Neuropharmacology. 2013 Sep;72:204-14. doi: 10.1016/j.neuropharm.2013.04.047. Epub 2013 May 2.
Recent electrophysiological evidence suggests that ethanol simultaneously exerts opposite effects on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) through two parallel mechanisms, one promoting and the other reducing the GABA release onto VTA DA neurons. Here we explore the possible behavioural implications of these findings by investigating the role displayed by acetaldehyde (the main metabolite of ethanol) and the non-metabolized fraction of ethanol in motor activity of rats. We analyse the appearance of motor activation or depression after intra-VTA administration of ethanol in rats subjected to different pharmacological pre-treatments designed to preferentially test either the effects of acetaldehyde or the non-metabolized ethanol. Motor activity was evaluated after intra-VTA administration of 35 nmol of ethanol, an apparently ineffective dose that does not modify the motor activity of animals. Pharmacological pre-treatments were used in order to either increase (cyanamide, 10 mg/kg, ip) or decrease (D-penicillamine, 50 mg/kg, ip and sodium azide, 7 mg/kg, ip) acetaldehyde levels in the VTA. Pre-treatments aimed to augment acetaldehyde, increased motor activity of rats. Otherwise, pre-treatments intended to decrease local acetaldehyde levels evoked significant reductions in motor activity that were prevented by the local blockade (bicuculline, 17.5 pmol) of the GABAA receptors. Our findings suggest that the brain-generated acetaldehyde is involved in the stimulant effects of ethanol, whereas the non-biotransformed fraction of ethanol, acting through the GABAA receptors, would account for the depressant effects. The present behavioural findings suggest that ethanol dually modulates the activity of DA neurons.
最近的电生理学证据表明，乙醇通过两种平行机制对腹侧被盖区（VTA）中的多巴胺（DA）神经元的活动产生相反的影响，一种促进，另一种减少 GABA 对 VTA DA 神经元的释放。在这里，我们通过研究乙醛（乙醇的主要代谢物）和乙醇的非代谢部分在大鼠运动活动中的作用，探讨了这些发现的可能行为学意义。我们分析了在不同药理学预处理的大鼠中，VTA 内给予乙醇后，出现运动激活或运动抑制的情况，这些预处理旨在优先测试乙醛或非代谢乙醇的作用。在 VTA 内给予 35 nmol 的乙醇后评估运动活动，这是一种显然无效的剂量，不会改变动物的运动活动。使用药理学预处理来增加（氰酰胺，10 mg/kg，ip）或减少（D-青霉胺，50 mg/kg，ip 和叠氮化钠，7 mg/kg，ip）VTA 中的乙醛水平。旨在增加乙醛的预处理增加了大鼠的运动活动。相反，旨在降低局部乙醛水平的预处理会引起运动活动的显著减少，而局部阻断（荷包牡丹碱，17.5 pmol）GABAA 受体则可以预防这种减少。我们的发现表明，大脑产生的乙醛参与了乙醇的兴奋剂作用，而未生物转化的乙醇部分通过 GABAA 受体作用，会导致抑郁作用。目前的行为学发现表明，乙醇双重调节 DA 神经元的活性。
