Pre-exposure to eutylone attenuates its own aversive effects but has no impact on cocaine or MDMA: A possible role of eutylone's hybrid pharmacology.

Previous research has reported that pre-exposure to a variety of drugs of abuse can impact (reduce) the aversive effects of themselves and other abused compounds, often as a function of their shared pharmacological activity. In this context, the present series of studies investigated the effects of history with the synthetic cathinone eutylone on the aversive effects of cocaine, MDMA, and itself in adult, male Sprague-Dawley rats. Given eutylone's structural similarities with its parent compound methylone, it was predicted that its ability to attenuate cocaine- and MDMA-induced taste avoidance would parallel the effects of methylone pre-exposure in this design (cocaine > MDMA). In Experiment 1, male Sprague-Dawley rats were exposed to eutylone (20 mg/kg, IP) or equivolume saline every other day for five exposures followed by taste avoidance conditioning with 20 mg/kg cocaine (SC) or 1.8 mg/kg MDMA (SC). Both cocaine and MDMA induced significant taste avoidance that developed over repeated conditioning trials. Cocaine and MDMA-induced avoidance were unaffected by eutylone history. To assess the general ability of eutylone pre-exposure to attenuate taste avoidance conditioning in the pre-exposure design, in Experiment 2, an additional set of male Sprague-Dawley rats was injected with 20 mg/kg eutylone (IP) prior to taste avoidance conditioning with eutylone (20 mg/kg (IP). Under these conditions, eutylone-induced avoidance was attenuated by eutylone pre-exposure. Given that eutylone history attenuated eutylone-induced avoidance argues that the failure to affect cocaine or MDMA was not a function of eutylone in this preparation. The inability of eutylone to attenuate the aversive effects of cocaine and MDMA despite sharing pharmacological activity suggests that eutylone's hybrid pharmacology may create a unique interoceptive effect different than that produced by either drug.