Abuse-related effects of synthetic cathinones：importance of DAT/SERT relationships  

作　　者：Brenda M GANNON Michael H BAUMANN Kenner C RICE Gregory T COLLINS 

机构地区：[1]Department of Pharmacology,University of Texas Health Science Center,San Antonio,TX 78229 [2]Designer Drug Research Unit,Intramural Research Program,NIDA and NIH,Baltimore,MD 21224 [3]Drug Design and Synthesis Section,Molecular Targets and Medications Discovery Branch,NIDA and NIAAA,Bethesda,MD 20814 [4]South Texas Veterans Health Care System,San Antonio,TX 78229

出　　处：《中国药理学与毒理学杂志》2017年第10期951-951,共1页Chinese Journal of Pharmacology and Toxicology

基　　金：supported by NIH and NIDA(R01DA039146;T32DA031115);NIH Intramural Research Programs

摘　　要：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 secondgeneration 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 wasα-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.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 secondgeneration 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 wasα-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.

关 键 词：synthetic cathinones bath salts SELF-ADMINISTRATION dopamine transporter serotonin transporter 

分 类 号：R965[医药卫生—药理学]