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Mephedrone (4-methylmethcathinone, 'meow'): acute behavioural effects and distribution of Fos expression in
Craig P Motbey1, Glenn E Hunt, Michael T Bowen
1School of Psychology, University of Sydney, NSW 2006, Australia.
Abstract:
Mephedrone (4-methylmethcathinone) is a novel recreational drug that has rapidly increased in popularity in recent years. Users report mephedrone as having the stimulant-like qualities of methamphetamine and cocaine, combined with the prosocial, entactogenic effects of 3,4-methylenedioxymethamphetamine (MDMA). Anecdotal and case study reports indicate that mephedrone may have the potential to engender compulsive patterns of use as well as toxicity in overdose. However, there have been almost no neuropharmacological investigations of the drug up to this point. Here we examined the effects of two different mephedrone doses [15 and 30 mg/kg, intraperitoneal (IP)] relative to the well-known stimulant methamphetamine (2 mg/kg IP) in adolescent rats. Rats were injected, assessed for locomotor activity for 60 minutes and then tested in a 10-minute social preference test (measuring time spent in close proximity to a real rat versus a dummy rat). Their brains were then processed using Fos immunohistochemistry to determine patterns of brain activation. Results showed that mephedrone caused profound locomotor hyperactivity at both dose levels while tending to reduce social preference. Patterns of Fos expression with mephedrone resembled a combination of those observed with methamphetamine and MDMA, with particularly strong Fos expression in the cortex, dorsal and ventral striatum, ventral tegmental area (typical of both MDMA and methamphetamine) and supraoptic nucleus (typical of MDMA). These results demonstrate for the first time the powerful stimulant effects of mephedrone in animal models and its capacity to activate mesolimbic regions. These results also provide some empirical basis to user reports that mephedrone subjectively resembles a MDMA/methamphetamine hybrid.
Insights
Mephedrone, a popular recreational drug, significantly increases locomotor activity and reduces social preference in adolescent rats. Its neurochemical effects resemble a hybrid of methamphetamine and MDMA, validating user reports.
Area of Science:
- Neuropharmacology
- Psychopharmacology
- Behavioral Neuroscience
Background:
- Mephedrone (4-methylmethcathinone) is a novel recreational stimulant with increasing popularity.
- User reports suggest it combines stimulant, prosocial, and entactogenic effects.
- Limited neuropharmacological data exists despite potential for compulsive use and toxicity.
Purpose of the Study:
- To investigate the neuropharmacological effects of mephedrone in adolescent rats.
- To compare mephedrone's effects to methamphetamine.
- To examine mephedrone's impact on locomotor activity, social preference, and brain activation patterns.
Main Methods:
- Adolescent rats received intraperitoneal injections of mephedrone (15 and 30 mg/kg) or methamphetamine (2 mg/kg).
- Locomotor activity was assessed for 60 minutes post-injection.
- A social preference test and Fos immunohistochemistry were used to evaluate behavior and brain activation.
Main Results:
- Mephedrone induced significant locomotor hyperactivity at both tested doses.
- Mephedrone tended to decrease social preference in the rats.
- Fos expression patterns with mephedrone mimicked a combination of methamphetamine and MDMA effects, particularly in the striatum and ventral tegmental area.
Conclusions:
- Mephedrone exhibits potent stimulant effects in animal models.
- The drug activates key mesolimbic reward pathways.
- Findings provide empirical support for mephedrone's subjective resemblance to an MDMA/methamphetamine combination.

