摘要
The mesolimbic dopamine system consisting of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (N.Acc.) mediates the reinforcing effects of addictive drugs including alcohol. Given that VTA is a heterogeneous area and that alcohol, in rather low doses, interacts directly with ligand-gated ion channels, we hypothesised that low, rather than high, doses of alcohol into the VTA activate the mesolimbic dopamine system and that alcohol may have different effects in the anterior and posterior parts of the VTA. The present study was undertaken to investigate this hypothesis. The present series of experiment show that infusion of a low dose of alcohol (20 mM) into the anterior, but not posterior, part of the VTA increases accumbal dopamine release in rats. In addition, higher doses of alcohol (100 or 300 mM) into the anterior or posterior part of the VTA do not affect the release of dopamine in the N.Acc., suggesting that low doses of alcohol can activate the mesolimbic dopamine system via mechanisms in the VTA. These data contribute to understanding the neuronal mechanisms underlying the dependence-producing properties of alcohol and could tentatively contribute to that new treatment strategies for alcohol use disorder can be developed.
The mesolimbic dopamine system consisting of dopaminergic neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (N.Acc.) mediates the reinforcing effects of addictive drugs including alcohol. Given that VTA is a heterogeneous area and that alcohol, in rather low doses, interacts directly with ligand-gated ion channels, we hypothesised that low, rather than high, doses of alcohol into the VTA activate the mesolimbic dopamine system and that alcohol may have different effects in the anterior and posterior parts of the VTA. The present study was undertaken to investigate this hypothesis. The present series of experiment show that infusion of a low dose of alcohol (20 mM) into the anterior, but not posterior, part of the VTA increases accumbal dopamine release in rats. In addition, higher doses of alcohol (100 or 300 mM) into the anterior or posterior part of the VTA do not affect the release of dopamine in the N.Acc., suggesting that low doses of alcohol can activate the mesolimbic dopamine system via mechanisms in the VTA. These data contribute to understanding the neuronal mechanisms underlying the dependence-producing properties of alcohol and could tentatively contribute to that new treatment strategies for alcohol use disorder can be developed.
基金
grants from the Swedish Research Council (grant no. K2006-21X-04247-33-3 and 2009-2782)
The Swedish brain foundation, LUA/ALF (grant no. 148251)
