Effects of Methylone Pre-Exposure on Fluoxetine-Induced Conditioned Taste Avoidance in Male and Female Sprague-Dawley Rats

Background: Prior work has reported that a drug's aversive effects (as indexed by taste avoidance conditioning) are attenuated when the pre-exposure and conditioning drugs are the same or different. The latter, otherwise known as cross-drug pre-exposure, is especially interesting as it has been used as a tool to assess mechanisms underlying the aversive effects of drugs. We previously reported that methylone pre-exposure differentially impacted the aversive effects of MDPV and MDMA (MDPV > MDMA), a difference consistent with the dopaminergic mediation of methylone's aversive effects. To examine the possible role of serotonin (5-HT) in methylone's aversive effects, the present study assessed the effects of methylone pre-exposure on taste avoidance induced by the 5-HT reuptake inhibitor fluoxetine. Methods: Male and female Sprague-Dawley rats were exposed to 10 mg/kg of methylone every 4th day (for a total of 5 injections) prior to taste avoidance training with 10 mg/kg of fluoxetine. Results: Fluoxetine induced significant taste avoidance (each p < 0.05) that was independent of sex. Methylone pre-exposure had no impact on avoidance produced by fluoxetine in either males or females (each p > 0.05). Conclusions: Methylone pre-exposure had no impact on fluoxetine-induced avoidance. These findings suggest that it is unlikely that 5-HT mediates the aversive effects of methylone. The implications of the present results for the mechanisms mediating methylone's aversive effects were discussed. Understanding such mechanisms is important in predictions relevant to drug history and abuse liability as a variety of subject and experiential factors known to affect (reduce) a drug's aversive effects may increase its use and potential for abuse.