Abuse-related effects of synthetic cathinones:importance of DAT/SERT relationships / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE Wide spread abuse of synthetic cathinones found in bath salts preparations has resulted in regulation of some cathinones internationally. Chemists skirt these laws by altering the chemical structures of first-generation cathinones (ie, MDPV, methylone, and mephedrone), resulting in second-generation cathinones (eg, α-PVP, α-PPP, MDPPP, and MDPBP). Although MDPV is a more effective reinforcer than cocaine, little is known about the reinforcing effectiveness of second-generation cathinones. To test the hypothesis that synthetic cathinones with higher selectivity for DAT relative to SERT are more effective reinforcers. METHODS Monoamine transporter inhibition was determined using synaptosomes prepared from rat brains. The relative reinforcing effectiveness of intravenously self-administered MDPV, MDPBP, MDPPP, α-PVP, α-PPP, and cocaine were directly compared through evaluations of ① dose- response curves under a progressive ratio (PR) schedule of reinforcement and ② demand curves obtained for each drug in male Sprague-Dawley rats. RESULTS Rank order selectivity for DAT/SERT was α-PVP>MDPV>α-PPP≈MDPBP>MDPPP>cocaine. Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement (α-PVP>MDPV>α-PPP>MDPBP≈MDPPP>cocaine) and the essential value obtained for each drug in demand analyses (α-PVP>MDPV>α-PPP≈MDPBP≈MDPPP>cocaine) suggest relative reinforcing effectiveness is related to DAT/SERT selectivity. CONCLUSION These data provide evidence that DAT/SERT selectivity accounts for select synthetic cathinones functioning as more effective reinforcers than cocaine and may predict the abuse-related effects of novel synthetic cathinones in humans.