The dopamine D3 receptor plays an essential role in alcohol-seeking and relapse.
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
Valentina
V
Department of Psychopharmacology, Central Institute of Mental Health, Mannheim, Germany. valentina.vengeliene@zi-mannheim.de
Leonardi-Essmann
Fernando
F
Perreau-Lenz
Stephanie
S
Gebicke-Haerter
Peter
P
Drescher
Karla
K
Gross
Gerhard
G
Spanagel
Rainer
R
D000428:Alcohol Drinking / Q000235:genetics; D000437:Alcoholism / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D001921:Brain / Q000502:physiology / Q000503:physiopathology; D002421:Caudate Nucleus / Q000502:physiology / Q000503:physiopathology; D003463:Cues; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D008297:Male; D009570:Nitriles / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000502:physiology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000235:genetics*; D012008:Recurrence; D044005:Tetrahydroisoquinolines / Q000494:pharmacology
D009570:Nitriles; D050637:Receptors, Dopamine D3; C409982:SB 277011; D044005:Tetrahydroisoquinolines