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Acetaldehyde mediates alcohol activation of the mesolimbic dopamine system

Melis, Miriam and Enrico, Paolo and Peana, Alessandra Tiziana and Diana, Marco (2007) Acetaldehyde mediates alcohol activation of the mesolimbic dopamine system. European Journal of Neuroscience, Vol. 26 (10), p. 2824-2833. eISSN 1460-9568. Article.

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DOI: 10.1111/j.1460-9568.2007.05887.x

Abstract

Ethanol (EtOH), the main psychoactive ingredient of alcoholic drinks, is widely considered to be responsible for alcohol abuse and alcoholism through its positive motivational properties, which depend, at least partially, on the activation of the mesolimbic dopaminergic system. However, acetaldehyde (ACD), the first metabolite of EtOH, has been classically considered to be aversive and useful in the pharmacological therapy of alcoholics. Here we show that EtOH-derived ACD is necessary for EtOH-induced place preference, a pre-clinical test with high predictive validity for reward liability. We also found that ACD is essential for EtOH-increased microdialysate dopamine (DA) levels in the rat nucleus accumbens and that this effect is mimicked by intra-ventral tegmental area (VTA) ACD administration. Furthermore, in vitro, ACD enhances VTA DA neuronal firing through action on two ionic currents: reduction of the A-type K+ current and activation of the hyperpolarization-activated inward current. EtOH-stimulating properties on DA neurons are prevented by pharmacological blockade of local catalase, the main metabolic step for biotransformation of EtOH into ACD in the central nervous system. These results provide in-vivo and in-vitro evidence for a key role of ACD in the motivational properties of EtOH and its activation of the mesolimbic DA system. Additionally, these observations suggest that ACD, by increasing VTA DA neuronal activity, would oppose its well-known peripherally originating aversive properties. Careful consideration of these findings could help in devising new effective pharmacological therapies aimed at reducing EtOH intake in alcoholics.

Item Type:Article
ID Code:2453
Status:Published
Refereed:Yes
Uncontrolled Keywords:Addiction, alcoholism, conditioned place preference, electrophysiology, microdialysis, rat
Subjects:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
001 Università di Sassari > 01 Dipartimenti > Scienze del farmaco
Publisher:Blackwell Science / Wiley
eISSN:1460-9568
Copyright Holders:© The Authors (2007). Journal Compilation, © Federation of European Neuroscience Societies and Blackwell
Deposited On:18 Aug 2009 10:07

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