The role of acetaldehyde in the ethanol-induced increase in dopamine release in the Nucleus Accumbens. In vivo microdialysis

Previous evidence shows that acetaldehyde (ACD), the main metabolite of alcohol previously considered only a toxic substance, may participate in mediating some of the reinforcing effects of ethanol (EtOH) (1). Accordingly, in rodents ACD is self-administered in the Ventral Tegmental Area (VTA) and stimulates the firing rate of mesolimbic dopaminergic neurons (2,3). Moreover, recent data show that ACD functional blockade, by sequestration with D- penicillamine, or by administration of alcohol dehydrogenase competitive inhibition with 4-methylpyrazole, prevents electrophysiological and behavioral effects of EtOH (3,4). In this study, we used in vivo microdialysis to measure dopamine (DA) output in the Nucleus Accumbens shell (Nacbs) of male albino Wistar rats in response to a challenge with ACD and EtOH. Both EtOH (0.5, 1.0, 2.0 g/kg) and ACD (10, 20, 40 mg/kg) were administered by gavage (i.g.) in order to mimic the route of administration used by humans. To evaluate the role of VTA, ACD (50, 75, 100 μM) was administered via reverse dialysis within the VTA while measuring DA output in the Nacbs. Intragastric EtOH and ACD administration dose-dependently increased DA extracellular levels in the Nacbs; similar results were obtained with intra-VTA ACD administration. Interestingly, ACD (i.g. administration) was more potent than EtOH, eliciting similar effects on DA outflow in the Nacbs at doses 50-fold lower. These findings support the hypothesis that ACD has central effects in its own right and show that ACD stimulates mesolimbic DAergic neurons by an intra- VTA mechanism, thereby contributing to the EtOH-induced increment in DA outflow in the NAcbs. Our results, together with the data in the literature, allows to conclude that ACD plays a key role in the EtOH-induced stimulation of mesolimbic pathway and possibly in its rewarding and motivational properties. 1) Quertemont et Al., TIPS 25(3):130-4, 2004 2) Rodd-Henricks et Al., PBB 72:55-64, 2002 3) Foddai et Al., Neuropsych. 29(3): 530-6, 2004 4) Font et Al., Neuropsych. 184(1): 56-64, 2005