Mephedrone, compared with MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and 5-HT levels in nucleus accumbens of awake rats

Abstract

BACKGROUND AND PURPOSEThe designer drug 1-(4-methylphenyl)-2-methylaminopropan-1-one (4-methylmethcathinone, mephedrone) is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine (DA) and 5-HT in the nucleus accumbens of awake rats and compare these effects with those induced by 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) and amphetamine. EXPERIMENTAL APPROACHMicrodialysis sampling was performed while simultaneously recording locomotor activity in rats and the monoamines were determined by HPLC with electrochemical detection. KEY RESULTSMephedrone (3 mg·kg -1 s.c.) and (+)-amphetamine (1 mg·kg -1 s.c.) caused rapid increases in extracellular DA levels of 496% and 412%, respectively, whereas MDMA (3 mg·kg -1 s.c.) showed only a moderate effect (235%). The corresponding 5-HT levels increased to 941% (mephedrone) and 911% (MDMA), but only to 165% following amphetamine. The calculated t1/2 values for elimination rate of mephedrone, MDMA and amphetamine-induced increases in extracellular DA levels were 25, 303 and 51 min, the corresponding t1/2 values for 5-HT were 26, 48 and 84 min, respectively. Locomotor activity was increased most by amphetamine, whereas both mephedrone and MDMA showed about three times lower and shorter-lasting effects. CONCLUSIONS AND IMPLICATIONSThe neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine-like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent re-inforcing properties.

Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone

“…It increases extracellular dopamine and to an even greater extent 5-HT in the nucleus accumbens (Baumann et al, 2012;Eshleman et al, 2013;Kehr et al, 2011;Wright et al, 2012). The current study, in contrast, suggests that in the striatum, the percentage increase in 5-HT and dopamine is rather similar, at least after the second and third injections.…”

“…Once transported into the cell mephedrone stimulates neurotransmitter release and disrupts vesicular storage by interaction with the vesicular monoamine transporter (VMAT) and can also stimulate non-exocytotic release by reversing the monoamine transporter flux (Simmler et al, 2013). Consistent with this, systemic mephedrone administration to freely moving rats elevates extracellular levels of dopamine, and to a greater extent 5-HT, in the nucleus accumbens (Baumann et al, 2012;Kehr et al, 2011;Wright et al, 2012).…”

“…Mephedrone induces hyperactivity in rodents following both acute and intermittent administration (Angoa-Perez et al, 2012;Baumann et al, 2012;Kehr et al, 2011;Marusich et al, 2012;Shortall et al, 2013b;Wright et al, 2012). Mephedrone (0.5 to 30 mg/kg i.p.…”

Powerful Cocaine-Like Actions of 3,4-Methylenedioxypyrovalerone (MDPV), a Principal Constituent of Psychoactive ‘Bath Salts’ Products

“…There are notable differences in transporter selectivity across this group of compounds as well. Mephedrone and methylone are non-selective transporter substrates that produce neurochemical effects akin to those produced by MDMA (Baumann et al, 2012;Kehr et al, 2011). By contrast, MDPV is a catecholamine-selective uptake blocker.…”

Human Pharmacology of Mephedrone in Comparison with MDMA

“…Studies in animal models indicate that mephedrone acts as a monoamine releaser and a reuptake inhibitor (Simmler et al, 2013;Baumann et al, 2012;López-Arnau et al, 2012). It has, therefore, been shown to increase dopamine in a similar manner to amphetamine and produce more serotonin increase (5-HT) than MDMA (Baumann et al, 2012;Kehr et al, 2011). The profile of mephedrone action on monoamine receptors and transporters suggests it could have a high abuse liability, and several studies have found that it supports self-administration at a higher rate than MDMA (Green et al, 2014).…”