Accumbal dopamine D2 receptor function is associated with individual variability in ethanol behavioral sensitization

Striatal dopamine D2 receptors have been implicated in the development of behavioral sensitization after repeated exposure to drugs of abuse. There are clear individual differences in the level of sensitization to ethanol among species and even among individuals from the same strain. Albino Swiss mice treated with ethanol (2.2 g/kg) have been shown to present clear variations in the development of sensitization. While some mice developed ethanol (EtOH) induced sensitization, others did not. This variability was associated with differences in D2 dopaminergic receptor binding. In the present study, we evaluated the functional relevance of dopamine D2 receptor by measuring, in sensitized and non-sensitized mice, the locomotor response to a D2 receptor agonist (quinpirole, 0.5 and 2.0 mg/kg i.p. or 0.01 and 0.2 mu g/side intra-accumbens) or antagonist (sulpiride, 10 or 50 mg/kg i.p. or 0.02 mu g/side intra-accumbens + ethanol i.p.). Whereas the systemic administration of quinpirole decreased locomotor activity in a similar way in all the groups, intra-nucleus accumbens (NAc) administration induced significantly higher locomotor stimulation in the sensitized group alone. Our data show that functionally hyperresponsive D2 receptors are present in the NAcs of sensitized but not non-sensitized mice, suggesting that this could be a biomarker of behavioral sensitization. Furthermore, i.p. administration of sulpiride blocked the expression of sensitization in the sensitized group, and intra-NAc administration attenuated it, indicating that the activation of accumbal D2 receptors is essential for the expression of EtOH behavioral sensitization. This article is part of a Special Issue entitled `Post-Traumatic Stress Disorder'. (C) 2011 Elsevier Ltd. All rights reserved. (AU)