Methylone pre-exposure differentially impacts the aversive effects of MDPV and MDMA in male and female Sprague-Dawley rats Implications for abuse vulnerability.
Polydrug use is well documented in synthetic cathinone users, although the consequences of such use are not well characterized. In pre-clinical research, a pre-exposure to a drug has been reported to attenuate the aversive effects of other drugs which has implications for their abuse potential. The goal of the present study was to investigate the impact of pre-exposure to the synthetic cathinone methylone on the aversive effects of MDPV and MDMA. Male and female Sprague-Dawley rats were exposed to 10 mgkg of methylone every 4th day (for a total of five injections) prior to taste avoidance training with 1.8 mgkg of MDPV or 1 mgkg of MDMA. MDPV and MDMA induced taste avoidance in males and females (all ps < 0.05). In males, methylone pre-exposure attenuated the avoidance induced by MDPV and MDMA (all ps < 0.05) with the attenuation greater with MDPV. In females, methylone pre-exposure attenuated avoidance induced by MDPV (all ps < 0.05), but it had no effect on those induced by MDMA (all ps > 0.05). The effects of exposure to methylone on taste avoidance induced by MDPV and MDMA were drug- (MDPV > MDMA) and sex- (MDMA only in males) dependent. The attenuating effects of methylone pre-exposure on MDPV and MDMA were discussed in terms of their shared neurochemical action. These findings suggest that a history of methylone use may reduce the aversive effects of MDPV and MDMA which may have implications for polydrug use involving the synthetic cathinones.