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 

作者机构：Department of PharmacologyUniversity of Texas Health Science CenterSan AntonioTX 78229 Designer Drug Research UnitIntramural Research ProgramNIDA and NIHBaltimoreMD 21224 Drug Design and Synthesis SectionMolecular Targets and Medications Discovery BranchNIDA and NIAAABethesdaMD 20814 South Texas Veterans Health Care SystemSan AntonioTX 78229 

出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)

年 卷 期：2017年第31卷第10期

页      面：951-951页

核心收录：

学科分类：1006[医学-中西医结合] 10[医学] 100602[医学-中西医结合临床] 

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

主　　题：synthetic cathinones bath salts self-administration dopamine transporter serotonin transporter 

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-PVPMDPVα-PPP≈MDPBPMDPPPcocaine.Comparisons of the maximum number of infusions obtained under a PR schedule of reinforcement(α-PVPMDPVα-PPPMDPBP≈MDPPPcocaine)and the essential value obtained for each drug in demand analyses(α-PVPMDPVα-PPP≈MDPBP≈MDPPPcocaine)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.