The selective agonist of dopamine D2 receptors cabergoline decreases alcohol consumption and increases the level of DRD2 mRNA in the brain of rats with chronic alcohol intoxication

Cabergoline is a high-affinity agonist of dopamine receptors of the second type (DRD2). Activation of these receptors plays a considerable role in the regulation of dopamine neurotransmission, whose disruption is considered as one of the major mechanisms of formation of alcohol motivation. Here, we studied the effect of cabergoline on alcohol consumption and the level of DRD2 mRNA in the brain of chronically alcoholized animals. We used mature Wistar rats with high level of alcohol consumption (over 6 g/kg per day) that were selected after testing in a “free choice” model (10% ethanol solution vs water) after 3 months of forced alcoholization (a 10% ethanol solution as a single source for drinking). Cabergoline (0.5 mg/kg intraperitoneally, once in a day, n = 9) or vehicle (n = 8) were administered under conditions of “free choice” and daily registration of alcohol consumption during 24 days. In 24 h after the last injection of cabergoline, animals were decapitated. Analysis of the level of DRD2 mRNA in the midbrain and striatum was performed after reverse transcription quantitative polymerase chain reaction (RT-qPCR). To elucidate the influence of cabergoline on DRD2 mRNA in the brain of rats without chronic alcohol intoxication, we used a control group of animals of an identical age that were treated with cabergoline (0.5 mg/kg, n = 10) or vehicle (n = 9) for 24 days. We found that cabergoline decreases ethanol consumption and increases the level of DRD2 mRNA in the midbrain and striatum of rats with chronic alcohol intoxication. In the control (non-alcoholized) animals, no significant changes in the DRD2 mRNA level were observed during cabergoline administration. It is possible to hypothesize that regulation of DRD2 at the level of transcription may underlie the observed decrease in the alcohol motivation and cabergoline may be proposed for future analysis as a potential medication for treatment of alcohol dependence.