Evaluating Preference-Seeking and Aversive Qualities of Salvia divinorum and Mitragyna speciosa

Abstract

Use of botanicals for self-diagnosed conditions or recreational purposes is increasing. Many readily available botanicals are under-researched and little is known about potential liabilities. This study sought to utilize Conditioned Place Preference (CPP) to quantify rewarding or aversive properties of botanicals and their constituents in rats. This paradigm is based on the notion that animals prefer distinct environments previously paired with rewarding drugs [1]. Our approach to broadly characterize a botanical and its many constituents entails dose response functions of a plant extract, its fractions, and primary constituent(s). As a proof of concept, we chose two popular botanicals [2], one expected to produce place preference (Mitragyna speciosa) and the other expected to produce place aversion (Salvia divinorum). Because salvinorin A is well characterized as the major psychoactive compound, we did not study an extract fraction for S. divinorum. Following apparatus habituation and quantification of baseline compartment preference, male Sprague-Dawley rats were given eight drug-compartment conditioning trials which involved alternate day pairings of test compound to one compartment and vehicle to the other. This was followed by a compartment preference trial conducted under drug-free states. As expected, rats showed place preference to mitragynine similar to that of 1mg/kg (+)-Amphetamine. This effect was much less pronounced with the extract and its fractions. Rats showed robust place aversion to both Salvia divinorum and salvinorin A. These findings suggest that products that contain significant quantities of mitragynine pose a potential abuse liability.