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The dopamine D3 receptor plays an essential role in alcohol-seeking and relapse

Valentina Vengeliene^*,1,2, Fernando Leonardi-Essmann^*,1, Stephanie Perreau-Lenz^*, Peter Gebicke-Haerter^*, Karla Drescher, Gerhard Gross and Rainer Spanagel^*

^* Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany; and

Neuroscience Discovery Research, Abbott, Ludwigshafen, Germany

²Correspondence: Department of Psychopharmacology, University of Heidelberg, Central Institute of Mental Health (CIMH), J5, 68159 Mannheim, Germany. E-mail: valentina.vengeliene{at}zi-mannheim.de

Our study aimed to identify new candidate genes, which might be involved in alcohol craving and relapse. To find changes in gene expression after long-term alcohol consumption, we studied gene expression profiles in the striatal dopamine system by using DNA microarrays of two different alcohol-preferring rat lines (HAD and P). Our data revealed an up-regulation of the dopamine D3 receptor (D3R) after 1 yr of voluntary alcohol consumption in the striatum of alcohol preferring rats that was confirmed by qRT-polymerase chain reaction. This finding was further supported by the finding of up-regulated striatal D3R mRNA in nonselected Wistar rats after long-term alcohol consumption when compared with age-matched control animals. We further examined the role of the D3R in mediating alcohol relapse behavior using the alcohol deprivation effect (ADE) model in long-term alcohol drinking Wistar rats and the model of cue-induced reinstatement of alcohol-seeking behavior using the selective D3R antagonist SB-277011-A (0, 1, 3, and 10 mg/kg) and the partial agonist BP 897 (0, 0.1, 1, and 3 mg/kg). Both treatments caused a dose-dependent reduction of relapse-like drinking in the ADE model as well as a decrease in cue-induced ethanol-seeking behavior. We conclude that long-term alcohol consumption leads to an up-regulation of the dopamine D3R that may contribute to alcohol-seeking and relapse. We therefore suggest that selective antagonists of this pharmacological target provide a specific treatment approach to reduce alcohol craving and relapse behavior.—Vengeliene, V., Leonardi-Essmann, F., Perreau-Lenz, S., Gebicke-Haerter, P., Drescher, K., Gross, G., Spanagel, R. The dopamine D3 receptor plays an essential role in alcohol-seeking and relapse.

Key Words: gene expression profiling • alcohol deprivation effect • cue-induced reinstatement of ethanol-seeking behavior

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