Abstract
The drug 4-methylmethcathinone (4-MMC; aka, mephedrone, MMCAT, “plant food”, “bath salts”) is a recent addition to the list of popular recreational psychomotor-stimulant compounds. Relatively little information about this drug is available in the scientific literature, but popular media reports have driven recent drug control actions in the UK and several US States. Online user reports of subjective similarity to 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) prompted the current investigation of the thermoregulatory and locomotor effects of 4-MMC. Male Wistar and Sprague-Dawley rats were monitored after subcutaneous administration of 4-MMC (1–10 mg/kg ) using an implantable radiotelemetry system under conditions of low (23°C) and high (27°C) ambient temperature. A reliable reduction of body temperature was produced by 4-MMC in Wistar rats at 23°C or 27°C with only minimal effect in Sprague-Dawley rats. Increased locomotor activity was observed after 4-MMC administration in both strains with significantly more activity produced in the Sprague-Dawley strain. The 10 mg/kg s.c. dose evoked greater increase in extracellular serotonin, compared with dopamine, in the nucleus accumbens. Follow-up studies confirmed that the degree of locomotor stimulation produced by 10 mg/kg 4-MMC was nearly identical to that produced by 1 mg/kg d-methamphetamine in each strain. Furthermore, hypothermia produced by the serotonin 1A/7 receptor agonist 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) was similar in each strain. These results show that the cathinone analog 4-MMC exhibits thermoregulatory and locomotor properties that are distinct from those established for methamphetamine or MDMA in prior work, despite recent evidence of neuropharmacological similarity with MDMA.
Highlights
Discussions of the recreational drug 4-methylmethcathinone (4-MMC; mephedrone, ‘‘miaow-miaow’’, MMCAT, etc.) started to increase in online user forums such as bluelight.ru in 2008 [1]
Probe placements were verified histologically at the conclusion of the study. These experiments constitute a comprehensive investigation into the thermoregulatory and locomotor stimulant properties of 4-methylmethcathinone (4-MMC; aka mephedrone, MMCAT, ‘‘plant food’’), a drug which is being used recreationally by humans [8,9,35]
It was found that 4-MMC is efficacious as d-methamphetamine (METH) in stimulating locomotion, it was about tenfold less potent than METH
Summary
Discussions of the recreational drug 4-methylmethcathinone (4-MMC; mephedrone, ‘‘miaow-miaow’’, MMCAT, etc.) started to increase in online user forums such as bluelight.ru in 2008 [1]. About 15% of one experienced-user sample reported cold extremities while 67% reported excessive perspiration as a consequence of using mephedrone [14] This mixed effect on thermoregulation is reminiscent of 3,4-methylenedioxymethamphetamine which can produce elevated or reduced body temperature in rats, depending on the ambient temperature and the dose administered [15,16]; MDMA has been shown to restrict blood flow to the periphery in rabbits [17] and rats [18]. A repeated, high-dose binge exposure regimen under high ambient temperature resulted in hyperthermia, decreases in serotonin and SERT function in the hippocampus but did not alter dopamine content or DAT function in the striatum [10] Together these initial findings are similar to prior reports for MDMA [24,25,26]. Experiments were conducted in two common strains of laboratory rat (Wistar, Sprague-Dawley) to determine the generality of the effects
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