A critical evaluation of tetrahydroisoquinoline induced ethanol preference in rats.

It has been reported that certain tetrahydroisoquinoline compounds, especially salsolinol and tetrahydropaveroline (THP) when infused into the lateral ventricle of rats' brains results in increased preference for alcohol solutions. The effect is reported to be long-term, in that animals do not return to baseline drinking even months later. The current report provides a replicatin of the original experiments and also an extension of the work to complete dose-response curves for salsolinol and THP. Generally we have confirmed that rats of the Sprague-Dawley and Long-Evans strains do increase their alcohol intake in response to infused THP or salsolinol and that the effect is long lasting, up to 10 months. Such animals consume less alcohol at concentrations above 20% than below, in contrast to the previous reports where drinking was maintained at high concentrations of alcohol. While the animals will select alcohol in the face of a saccharin choice, they will not drink alcohol adulterated with quinine. We have failed to observe signs of dependence or withdrawal by these techniques and suggest that the original reports of these signs may have been a result of cellular damage caused by the long-term infusions. Additionally we have carried out extensive dose-response experiments with both salsolinol and THP. Doses of THP of 104 nmoles/day were inhibitory to alcohol drinking. We conclude that these compounds do shift these animals preference for alcohol relatively permanently, but not to the point of gross intoxication nor into the highly aversive range of alcohol concentration. We cannot confirm the reports that salsolinol or THP produce withdrawal symptoms when infused.