Mesolimbic dopamine system in alcohol-preferring rats.

The mesolimbic dopamine system of the brain, in particular the nucleus accumbens (Acb), is long known to be involved in reward behavior. When compared with the alcohol-nonpreferring NP rats, the alcohol-preferring P rats exhibit lower dopamine (DA) levels in the Acb as well as in other forebrain areas (20). In the present study, the DA innervation density, as determined by tyrosine hydroxylase (TH) immunostaining, was found lower in the selective cingulum cortex and the shell of the Acb of the P compared with that of NP rats. These structures cluster in the medial aspect of the mesolimbic system. There were no differences in other major DA mesolimbic brain regions. The subpopulation of DA neurons in the ventral tegmental area (VTA) projecting to the Acb was found to be smaller in the P than in the NP rats, as shown by horseradish peroxidase tracing and TH immunocytochemistry double staining. However, the total number of the DA neurons in the VTA, the major mesolimbic DA center, was found to be similar in the P and NP rats. These results indicate a selective reduction of catecholaminergic innervation in the dopaminergic medial mesolimbic system in the P rats and suggest that the P and NP rat lines should be a useful model for the investigation of DA involvement in alcohol drinking as well as other reinforced behaviors.