Eutylone history selectively impacts the rewarding and aversive effects of cocaine, MDMA, and eutylone in female Sprague-Dawley rats

Both the rewarding and aversive effects of a drug contribute to its abuse potential. One factor known to impact the balance of these effects is concurrent and serial polydrug use. A drug class for which such interactions are common is synthetic cathinones. In prior work, history with the synthetic cathinone eutylone had no effect on cocaine- or MDMA-induced taste avoidance in male rats, possibly as a function of the insufficient overlap between the pharmacological activity of eutylone and the other compounds. To investigate the broader scope of this effect, this study assessed how a history of eutylone influenced drug-induced taste avoidance in female rats. Assessments were also made on the rewarding effects of these drugs, given their importance for abuse vulnerability. In the present study, adult female Sprague-Dawley rats were exposed to eutylone or saline prior to concurrent taste avoidance/place preference conditioning in which saccharin and a distinct compartment were repeatedly paired with cocaine, MDMA, or eutylone. All drugs induced taste avoidance. Avoidance induced by eutylone was attenuated by eutylone history, but those induced by MDMA and cocaine were unaffected. Eutylone history had no effect on place preferences induced by MDMA or eutylone (but increased place preferences induced by cocaine). The failure of eutylone to impact the aversive effects of cocaine and MDMA despite sharing neurochemical actions suggests that eutylone's pharmacological activity may produce subjective effects that differ from those of either MDMA or cocaine. The differential effects of eutylone history on drug reward (increasing cocaine reward but having no impact on eutylone or MDMA) remain unknown but suggests that the basis for the aversive and rewarding effects of these drugs are dissociable.