Chronic infusion of tetrahydropapaveroline: A behavioral and biochemical model of ethanol addiction
Tetrahydropapaveroline (THP), one of a class of tetrahydroisoquinolines (TIQ's), may form peripherally following ingestion of ethanol by a condensation reaction of acetaldehyde with peripheral catecholamines. Experiments have shown that THP may cross the blood-brain barrier. Evidence suggests that the behavioral effects may be mediated by a central site of action. However alterations in ethanol consumption following chronic, peripheral infusion of THP, have not been shown previously. This was the central question addressed by the current research. Prior to experimental testing a test was performed to screen out animals having an ethanol preference. During testing, osmotic minipumps administered THP either subcutaneously or intravenously at a rate of 0.5 [Special characters omitted.] l/hour. Past research suggests a link between opioid modulation of the mesolimbic dopamine circuit and the behavioral action of THP. Therefore, after investigating the effects of THP on ethanol consumption, we evaluated the effect of naloxone on ethanol consumption following peripheral THP administration. Peripheral administration employing iv (intravenous) routes showed no significant differences between 2 [Special characters omitted.] g/[Special characters omitted.] l and 4 [Special characters omitted.] g/[Special characters omitted.] l concentrations. Means of 0.4869 and 0.4451 ml's 100% ethanol (i.e. 2 [Special characters omitted.] g/[Special characters omitted.] l and 4 [Special characters omitted.] g/[Special characters omitted.] l respectively) when compared to a baseline mean of 0.6672 ml's 100% ethanol obtained in the screening tests indicate a failure to produce increased ethanol consumption via iv route at the doses selected. With subcutaneous pump implants containing 0.0, 0.5, 1.0, 2.0, and 4.0 [Special characters omitted.] g/[Special characters omitted.] l, an inverse trend in ethanol consumption was noted; means were respectively 0.6522, 0.6130, 0.6468, 0.5473, and 0.4540. The proportion of consumed ethanol showed significant differences, F (4,45) = 2.799, p < .05. Using Fischer's LSD, groups receiving both 2 [Special characters omitted.] g/[Special characters omitted.] l THP, p < .05, and 4 [Special characters omitted.] g/[Special characters omitted.] l THP, p < .005, consumed a significantly smaller proportion of ethanol to water than did controls. The results were discussed in terms of the inverted U-shape dose-response curve, in which higher doses of THP lead to suppression of ethanol intake. During naloxone treatment, ethanol intake at baseline was not significantly different from intake during treatment. However, there was a significant increase in ethanol consumption at posttreatment, t (13) = 2.363, p < .05.