title: Escalation of intravenous self-administration of methylone and mephedrone under extended access conditions.
abstract: The recreational use of substituted cathinones continues to grow as a public health concern in the United States. Studies have shown that extended access to intravenous (i.v.) self-administration of stimulants, such as cocaine and methamphetamine, results in escalation of drug intake relative to shorter access; however, little is known about the impact of extended access on self-administration of entactogen class stimulants such as methylone and 4-methylmethcathinone (mephedrone). Male Wistar rats were randomly assigned to short-access (ShA, 2- h) and long-access (LgA, 6- h) groups and trained to self-administer methylone or mephedrone (0.5 mg/kg/infusion) using a fixed-ratio 1 response contingency. The methylone-trained groups were evaluated on a progressive-ratio (PR) procedure incorporating dose-substitution of methylone (0.125-2.5 mg/kg/infusion), mephedrone (0.125-2.5 mg/kg/infusion) or methamphetamine (MA; 0.01-0.5 mg/kg/infusion). Mephedrone-trained rats were similarly evaluated on a PR with mephedrone and MA. Rats trained with LgA to methylone and mephedrone earned more infusions during acquisition compared with ShA groups. Mephedrone-trained LgA rats reached significantly higher breakpoints than all other groups in mephedrone and MA PR tests. Methylone-trained LgA rats exhibited a rightward shift of the peak effective dose but no overall efficacy change compared with methylone-trained ShA rats. These findings show that the self-administration of mephedrone escalates under LgA conditions in a manner similar to traditional stimulants whereas escalation of 6 h intakes of methylone is not accompanied by differences in PR performance. Thus mephedrone represents the greater risk for dysregulated drug consumption.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Jacques D
authors.initials: JD
authors.lastname: Nguyen
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Yanabel
authors.initials: Y
authors.lastname: Grant
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Creehan
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Sophia A
authors.initials: SA
authors.lastname: Vandewater
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Taffe
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D001522:Behavior, Animal; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D003216:Conditioning, Operant; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration; D013997:Time Factors
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; C548233:mephedrone; C400939:methylone
keywords: bath salts; drug addiction; ecstasy; reward; substance abuse