Abstract
Mephedrone is a widely used drug of abuse, exerting its effects by interacting with monoamine transporters. Although this mechanism has been widely studied heretofore, little is known about the involvement of glutamatergic transmission in mephedrone effects. In this study, we comprehensively evaluated glutamatergic involvement in rewarding effects of mephedrone using an interdisciplinary approach including (1) behavioural study on effects of memantine (non-selective NMDA antagonist) on expression of mephedrone-induced conditioned place preference (CPP) in rats; (2) evaluation of glutamate concentrations in the hippocampus of rats following 6 days of mephedrone administration, using in vivo magnetic resonance spectroscopy (MRS); and (3) determination of glutamate levels in the hippocampus of rats treated with mephedrone and subjected to MRS, using ion-exchange chromatography. In the presented research, we confirmed priorly reported mephedrone-induced rewarding effects in the CPP paradigm and showed that memantine (5 mg/kg) was able to reverse the expression of this effect. MRS study showed that subchronic mephedrone administration increased glutamate level in the hippocampus when measured in vivo 24 h (5 mg/kg, 10 mg/kg and 20 mg/kg) and 2 weeks (5 mg/kg and 20 mg/kg) after last injection. Ex vivo chromatographic analysis did not show significant changes in hippocampal glutamate concentrations; however, it showed similar results as obtained in the MRS study proving its validity. Taken together, the presented study provides new insight into glutamatergic involvement in rewarding properties of mephedrone.
Highlights
Mephedrone (RS)-1-(4-methylphenyl)-2-metyloaminopropan-1-one is a synthetic derivative of cathinone, and its main compound is found in Catha edulis, a plant naturally grown mainly in East Africa [1]
Mephedrone represents the group of novel psychoactive substances (NPS) which consist of compounds designed to mimic existing established recreational drugs [2]
We evaluated the involvement of glutamatergic neurotransmission in the expression of mephedrone-induced conditioned place preference (CPP) via NMDA receptors using memantine
Summary
Mephedrone (RS)-1-(4-methylphenyl)-2-metyloaminopropan-1-one ( known as 4-metylometcatynon, 4-MMC, M-CAT) is a synthetic derivative of cathinone, and its main compound is found in Catha edulis, a plant naturally grown mainly in East Africa [1]. Mephedrone exerts its effects by interacting with plasma membrane monoamine transporter proteins for dopamine (DA) (dopamine transporter, DAT), noradrenaline (NA) (noradrenaline transporter, NET). Mephedrone causes a rapid and dose-dependent increase in both 5-HT and DA levels in the nucleus accumbens (NAc) [7, 8], striatum and frontal cortex in rats [7]. It has been shown that repeated mephedrone administration in binge-like regimen causes a rapid decrease in striatal DA and hippocampal 5-HT transporter function in mice which can be perceived as a neurotoxic effect [9]. Another study showed that mephedrone does not cause damage to striatum longlasting hippocampal 5-HT and DA nerve endings in mice. Mephedrone enhances the neurotoxic effects of amphetamine and MDMA on DA nerve endings [10, 11]. The effects of mephedrone can be potentiated because of its metabolites, which display a similar activity as mephedrone and an ability to interact with monoamine transporters, resulting in inhibition of their reuptake [14]
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