High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats

Neural consequences and comparison with methamphetamine

Craig P. Motbey, Kelly J. Clemens, Nadine Apetz, Adam R. Winstock, John Ramsey, Kong M. Li, Naomi Wyatt, Paul D. Callaghan, Michael T. Bowen, Jennifer L. Cornish, Iain S. McGregor*

*Corresponding author for this work

Research output: Contribution to journalArticle

68 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)823-836
Number of pages14
JournalJournal of Psychopharmacology
Volume27
Issue number9
DOIs
Publication statusPublished - Sep 2013

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