Mephedrone, an abused psychoactive component of 'bath salts' and methamphetamine congener, does not cause neurotoxicity to dopamine nerve endings of the striatum

• Published in: Journal of neurochemistry Vol. 120; no. 6; pp. 1097 - 1107
• Main Authors: Angoa-Pérez, Mariana, Kane, Michael J., Francescutti, Dina M., Sykes, Katherine E., Shah, Mrudang M., Mohammed, Abiy M., Thomas, David M., Kuhn, Donald M.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-03-2012; Wiley-Blackwell
• Subjects: Amphetamine; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Body Temperature - drug effects; Brain; Central nervous system; Central Nervous System Stimulants - pharmacology; Central neurotransmission. Neuromudulation. Pathways and receptors; Congeners; Corpus Striatum - cytology; Corpus Striatum - drug effects; Dopamine; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - metabolism; Dopamine transporter; Dopaminergic Neurons - cytology; Drug abuse; Drug addictions; Female; Fundamental and applied biological sciences. Psychology; Glial fibrillary acidic protein; Hyperthermia; Medical sciences; mephedrone; Methamphetamine; Methamphetamine - analogs & derivatives; Methamphetamine - pharmacology; Mice; Mice, Inbred C57BL; microglial activation; Neostriatum; Nerve endings; Nerve Endings - drug effects; Neurochemistry; Neuroglia - drug effects; Neurons; Neurotoxicity; Psychotropic drugs; Public health; Salts; Stimulants; Toxicity; Toxicology; Tyrosine 3-monooxygenase; Tyrosine 3-Monooxygenase - metabolism; Vertebrates: nervous system and sense organs; β-ketoamphetamines; Tyrosine; Dopamine; mephedrone; Glial fibrillary acidic protein; Rodentia; Central nervous system; Basal ganglion; Activation; Corpus striatum; β-ketoamphetamines; Catecholamine; Encephalon; Vertebrata; Nerve ending; Mammalia; Treatment; neurotoxicity; Mouse; methamphetamine; Light; Neurotransmitter; Hyperthermia; microglial activation
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07632.x

J. Neurochem. (2012) 120, 1097–1107.
Mephedrone (4‐methylmethcathinone) is a β‐ketoamphetamine with close structural analogy to substituted amphetamines and cathinone derivatives. Abuse of mephedrone has increased dramatically in recent years and has become a significant public health problem in the United States and Europe. Unfortunately, very little information is available on the pharmacological and neurochemical actions of mephedrone. In light of the proven abuse potential of mephedrone and considering its similarity to methamphetamine and methcathinone, it is particularly important to know if mephedrone shares with these agents an ability to cause damage to dopamine nerve endings of the striatum. Accordingly, we treated mice with a binge‐like regimen of mephedrone (4 × 20 or 40 mg/kg) and examined the striatum for evidence of neurotoxicity 2 or 7 days after treatment. While mephedrone caused hyperthermia and locomotor stimulation, it did not lower striatal levels of dopamine, tyrosine hydroxylase or the dopamine transporter under any of the treatment conditions used presently. Furthermore, mephedrone did not cause microglial activation in striatum nor did it increase glial fibrillary acidic protein levels. Taken together, these surprising results suggest that mephedrone, despite its numerous mechanistic overlaps with methamphetamine and the cathinone derivatives, does not cause neurotoxicity to dopamine nerve endings of the striatum.
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 Mephedrone, a psychoactive component of “bath salts”, is being abused increasingly throughout the US and Europe but it is not known if this agent is neurotoxic like its close structural congener methamphetamine. Mice treated with a binge‐like dosing regimen of mephedrone did not show signs of damage to dopamine nerve terminals despite developing significant hyperthermia and hyper‐locomotion, indices of increased synaptic dopamine. It appears that the addition to methamphetamine of a β‐keto group and a 4‐methyl substituent on the ring to yield mephedrone obviates the neurotoxicity caused by methamphetamine ingestion.