TL neuro

November 13, 2011

Mephedrone (4-MMC) at SfN on Sunday (11/13)

Filed under: Uncategorized — vapharmboy @ 8:20 am

Program # 263.02/Poster # DD31

Presentation Title: Mephedrone: Behavioural characterisation reveals amphetamine-like effects in the mouse

Time: Sunday, Nov 13, 2011, 2:00 PM – 3:00 PM

Mephedrone is a substituted cathinone which saw a rapid increase in use as a ‘legal high’ in the UK in 2009-2010 until its regulation under the UK Misuse of Drugs Act. Mephedrone has an amphetamine-like structure, but its mechanism of action remains unclear. There are many anecdotal reports of its effects but few scientific studies. The aim of the present study was to characterise the behavioural effects of mephedrone in mice.
Synthesis of (±)-mephedrone hydrobromide was achieved using the method reported by Sutcliffe et al. (J Pharm Biomed Anal, 2011, in press) in 67% yield.
24 male C57 Black 6/J mice (Harlan, UK) 8-9 weeks, 23.3 ± 0.4g, were allocated to treatment with 1 or 5 mg kg-1 mephedrone or saline vehicle ip, and underwent a series of behavioural tests to study: the effects of mephedrone on locomotor activity (LMA); mephedrone’s dependence liability using a conditioned place preference (CPP) paradigm; and the effects of chronic (21 day) mephedrone treatment on bodyweight and on sensorimotor gating as measured by pre-pulse inhibition (PPI).
2-way ANOVA followed by Bonferroni post-hoc tests revealed a significant increase in LMA induced by 5 mg kg-1 (p<0.01), but not by 1 mg kg-1 mephedrone. There was no effect of treatment on entries into or time spent in the open field centre square, suggesting no anxiety-like effects. In the CPP, pairing with mephedrone did not significantly shift the preference for the drug-paired side (% change in time spent in drug-paired side: veh 6.2 ± 4.9; mephedrone 1 mg kg-1 1.6 ± 4.8; 5 mg kg-1 3.3 ± 5.7). Thus we were unable to condition a place preference for mephedrone using a paradigm and mouse strain in which we have previously shown a place preference for d-amphetamine 1 mg kg-1. PPI was not significantly altered by chronic mephedrone at either dose 48 h or 2 weeks after the last drug treatment. Mice receiving daily 5 mg kg-1 mephedrone, unlike saline-treated animals, failed to gain weight over the first 12 days of chronic treatment (0.1 ± 1.7% increase vs 4.1 ± 0.8%, just missing significance, p= 0.085), with intermediate weight gain in 1 mg kg-1-treated mice. Weight gain was recovered during days 13-15.
These data indicate some amphetamine-like effects of mephedrone – increased locomotor activity and weight loss – but mephedrone appears rather less potent. The data show no detectable rewarding properties at the doses used and no psychosis-like disruption of sensorimotor gating after chronic treatment. Studies are under way in our laboratory to examine the mechanism of action of mephedrone and its derivatives


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