A re-evaluation of the role of tetrahydropapaveroline in ethanol consumption in rats

The role of tetrahydropapaveroline (THP), a condensation product of a dopaldehyde with dopamine, in the regulation of alcohol consumption was investigated. In the first experiment, rats received intraventricular injections of either racemic THP hydrobromide (0.65 or 1.3 μg/μl), R-(+)-THP (0.66 or 1.4 μg/μl), or an equal volume of vehicle. The lower doses of both (±)-THP and (+)-THP significantly increased volitional alcohol intake. For the racemic compound, the increase was significant at 7–13% concentrations. The R-(+)-enantiomer increased consumption at 4–11 and 15–20% concentrations of ethanol. The higher doses of both compounds did not significantly alter alcohol preference. A second experiment evaluated the chronic effect of THP delivered subcutaneously via osmotic minipump. Animals receiving THP (0.1, 0.5, 1.0, 2.0, and 4.0 mg/ml) did not differ in their alcohol intake, compared to vehicle-treated controls. Whether or not endogenously formed THP participates in the etiology of alcohol addiction remains unclear. Nonetheless, there are few known compounds that induce a preference for unsweetened alcohol solutions over water in laboratory animals.