Distribution of ubiquitin immunoreactivity in dopamine neurons of chronic alcoholics

In animal experiments drugs of abuse, including alcohol, have been shown to stimulate and affect dopamine neurons, which mediate their rewarding effects. In this study, the aim was to establish cellular effects of alcohol on human dopamine neurons, by investigating midbrain from 27 chronic alcoholics (33-84 years old) and 10 matched controls. We used polyclonal antibodies to ubiquitin, a marker which localizes lesions of the cellular stress caused by alcohol, on paraffin sections. Results showed that the grading of ubiquitin immunoreactivity (UBQ-IR) distribution differentiated two groups of alcoholics. The first was characterized by low average age and liver cirrhosis, the second by greater average age and absence of cirrhosis. In the first group UBQ-IR was distributed in dendrites and cell bodies of dopamine neurons, mostly along their membranes. In the second group dopamine neurons were negative, UBQ-IR was confined to dystrophic neurites in the neuropil. These data indicate that human dopamine neurons in chronic alcoholics of the first group, are metabolic targets of the stressful action of alcohol, revealed by UBQ-IR. The results also provide evidence that the second group of users, lacking cellular localization of UBQ-IR, have developed protective compensatory mechanisms to the membrane disruption caused by alcohol, due to a different genetic constitution.