Reduced TH-immunoreactive fibers in the limbic system of Sardinian alcohol-preferring rats.

The mesolimbic dopamine (DA) system has long been known to be involved in reward behaviors. As with other substances of abuse, it has been extensively reported that ethanol influences the dopaminergic system. The present study examined whether selectively bred Sardinian-alcohol-preferring (sP) and Sardinian alcohol non-preferring rats (sNP), differ in the DA innervation in structures of the forebrain that are related to rewarding behaviors. To this aim, we performed an immunohistochemistry study with an antibody raised against tyrosine hydroxylase (TH), the rate-limited step enzyme in the biosynthesis of monoamines. The TH-positive innervation density was found to be significantly lower in the cingulate cortex and in the shell of the nucleus accumbens of the sP when compared with the sNP and unselected Wistar rats. These anatomical structures both cluster in the medial aspect of the mesolimbic system. No differences in other major DA brain regions, such as the nigro-striatal pathway were found. The analysis of cell-body area revealed no differences between sP, sNP and Wistar rats in the ventral tegmental area and substantia nigra (pars compacta and reticulata) and the density of the TH-positive fibers was not different in the caudate-putamen. These results indicate a selective reduction of terminal innervation in the medial portion of the mesocorticolimbic DA system in sP rats and suggest that the latter may consume larger amounts of ethanol, when compared with sNP rats, to compensate for the deficiency of dopamine to produce an adequate level of reward.