High levels of intravenous mephedrone (4-methylmethcathinone) self-administration in rats: Neural consequences and comparison with methamphetamine

• Published in: Journal of psychopharmacology (Oxford) 2013-09, Vol.27 (9), p.823-836
• Main Authors: Motbey, Craig P, Clemens, Kelly J, Apetz, Nadine, Winstock, Adam R, Ramsey, John, Li, Kong M, Wyatt, Naomi, Callaghan, Paul D, Bowen, Michael T, Cornish, Jennifer L, McGregor, Iain S
• Format: Article
• Language: English
• Subjects: Administration, Intravenous - methods; Animals; Autoradiography; Biological and medical sciences; Brain; Dopamine; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - metabolism; Drug abuse; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medical sciences; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - adverse effects; Methamphetamine - analogs & derivatives; Motor Activity - drug effects; Neuropharmacology; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rodents; Self Administration - methods; Serotonin; Serotonin - metabolism
• ISSN: 0269-8811; 1461-7285
• DOI: 10.1177/0269881113490325

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.