title: High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: neural consequences and comparison with methamphetamine.
abstract: Mephedrone (MMC) is a relatively new recreational drug that has rapidly increased in popularity in recent years. This study explored the characteristics of intravenous MMC self-administration in the rat, with methamphetamine (METH) used as a comparator drug. Male Sprague-Dawley rats were trained to nose poke for intravenous MMC or METH in daily 2 h sessions over a 10 d acquisition period. Dose-response functions were then established under fixed- and progressive-ratio (FR and PR) schedules over three subsequent weeks of testing. Brains were analyzed ex vivo for striatal serotonin (5-HT) and dopamine (DA) levels and metabolites, while autoradiography assessed changes in the regional density of 5-HT and serotonin transporter (SERT) and DA transporter (DAT) and induction of the inflammation marker translocator protein (TSPO). Results showed that MMC was readily and vigorously self-administered via the intravenous route. Under a FR1 schedule, peak responding for MMC was obtained at 0.1 mg/kg/infusion, versus 0.01 mg/kg/infusion for METH. Break points under a PR schedule peaked at 1 mg/kg/infusion MMC versus 0.3 mg/kg/infusion for METH. Final intakes of MMC were 31.3 mg/kg/d compared to 4 mg/kg/d for METH. Rats self-administering MMC, but not METH, gained weight at a slower rate than control rats. METH, but not MMC, self-administration elevated TSPO receptor density in the nucleus accumbens and hippocampus, while MMC, but not METH, self-administration decreased striatal 5-hydroxyindolacetic acid (5-HIAA) concentrations. In summary, MMC supported high levels of self-administration, matching or exceeding those previously reported with other drugs of abuse.
authors.affiliation: School of Psychology, University of Sydney, Sydney, Australia.
authors.forename: Craig P
authors.initials: CP
authors.lastname: Motbey
authors.forename: Kelly J
authors.initials: KJ
authors.lastname: Clemens
authors.forename: Nadine
authors.initials: N
authors.lastname: Apetz
authors.forename: Adam R
authors.initials: AR
authors.lastname: Winstock
authors.forename: John
authors.initials: J
authors.lastname: Ramsey
authors.forename: Kong M
authors.initials: KM
authors.lastname: Li
authors.forename: Naomi
authors.initials: N
authors.lastname: Wyatt
authors.forename: Paul D
authors.initials: PD
authors.lastname: Callaghan
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bowen
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cornish
authors.forename: Iain S
authors.initials: IS
authors.lastname: McGregor
mesh_terms: D061605:Administration, Intravenous / Q000379:methods; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage* / Q000009:adverse effects* / Q000031:analogs & derivatives*; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000379:methods; D012701:Serotonin / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D012701:Serotonin; D008694:Methamphetamine; C548233:mephedrone; D004298:Dopamine
keywords: Mephedrone; addiction; autoradiography; neurotoxicity; self-administration