Altered brain sensitivity to ethanol in mice after MPTP treatment

Previous studies demonstrated the role of the dopaminergic receptors in brain sensitivity to ethanol. The present study was designed to assess the relative contribution of the nigrostriatal component to this brain sensitivity. Adult male C57BL mice were given 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) injections (30 mg/kg daily for 2 consecutive days). The treatment decreased the striatal dopamine level by 35% from the control level, and the number (Bmax) of dopaminergic receptors was increased by 67%. Ethanol-induced sleep time was reduced in the MPTP-treated mice, as compared to controls, and this gap progressively widened during the 3 weeks of testing to 29%. Brain ethanol levels upon awakening increased by 22%. The results suggest that the nigrostriatal dopaminergic pathways play a major role in determining brain sensitivity to ethanol which may represent an important component in the addictive process.