Comparative Evaluation of A Partial Dopamine Agonist with A Preferential D2 and D3 Receptor Antagonist on Ethanol Induced Conditioned Place Preference in Mice

Abstract

The role of dopamine receptor sub-families in the rewarding and reinforcing effects of drugs of abuse has been established in numerous studies. Objectives: In view of the extensive role of mesolimbic dopaminergic transmission in rewarding and reinforcing effect of abused drugs including ethanol, the present study evaluated three mechanistically different drugs viz a partial dopaminergic agonist (PDA, aripiprazole), preferential D3 (mixed D2/D3) receptor antagonist (nafadotride), and a preferential D2 antagonist (haloperidol), on ethanol-induced conditioned place preference (CPP) in mice. Method: The study was carried out in Swiss strain albino mice. Ethanol (20%, 2g/kg) was used to induce CPP in mice. After the acquisition of CPP, behavioral tests (elevated plus maze and locomotor activity) were conducted and effect of drugs on expression and on reinstatement (after extinction) was studied. We found that aripiprazole (1 and 2 mg/kg but not 0.5mg/kg), haloperidol (0.2 mg/kg), and nafadotride (4.5 mg/kg) administered for 1 week during the conditioning phase prevented acquisition, expression and reinstatement of ethanol-induced CPP. All the three drugs reduced the ethanol-induced locomotor stimulation and produced antianxiety effects in elevated plus maze following the acquisition of ethanol CPP. Partial dopaminergic agonism by aripiprazole was found to be a better strategy for normalizing dopaminergic neurotransmission in alcoholics as seen in rodents.