title: Stimulant mechanisms of cathinones - effects of mephedrone and other cathinones on basal and electrically evoked dopamine efflux in rat accumbens brain slices.
abstract: Mephedrone, an erstwhile "legal high", and some non-abused cathinones (ethcathinone, diethylpropion and bupropion) were tested for stimulant effects in vitro, through assessing their abilities to increase basal and electrically evoked dopamine efflux in rat accumbens brain slices, and compared with cocaine and amphetamine. We also tested mephedrone against cocaine in a dopamine transporter binding study. Dopamine efflux was electrically evoked and recorded using voltammetry in the rat accumbens core. We constructed concentration response curves for these cathinones for effects on basal dopamine levels; peak efflux after local electrical stimulation and the time-constant of the dopamine decay phase, an index of dopamine reuptake. We also examined competition between mephedrone or cocaine and [(125)I]RTI121 at the dopamine transporter. Mephedrone was less potent than cocaine at displacing [(125)I]RTI121. Mephedrone and amphetamine increased basal levels of dopamine in the absence of electrical stimulation. Cocaine, bupropion, diethylpropion and ethcathinone all increased the peak dopamine efflux after electrical stimulation and slowed dopamine reuptake. Cocaine was more potent than bupropion and ethcathinone, while diethylpropion was least potent. Notably, cocaine had the fastest onset of action. These data suggest that, with respect to dopamine efflux, mephedrone is more similar to amphetamine than cocaine. These findings also show that cocaine was more potent than bupropion and ethcathinone while diethylpropion was least potent. Mephedrone's binding to the dopamine transporter is consistent with stimulant effects but its potency was lower than that of cocaine. These findings confirm and further characterize stimulant properties of mephedrone and other cathinones in adolescent rat brain.
authors.affiliation: Department of Life Sciences, University of Roehampton, London SW15 4JD.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Opacka-Juffry
authors.affiliation: Pharmacology & Cell Physiology, Division of Biomedical Science, St George's, University of London, London SW17 0RE, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pinnell
authors.affiliation: Pharmacology & Cell Physiology, Division of Biomedical Science, St George's, University of London, London SW17 0RE, United Kingdom.
authors.forename: Nisha
authors.initials: N
authors.lastname: Patel
authors.affiliation: Pharmacology & Cell Physiology, Division of Biomedical Science, St George's, University of London, London SW17 0RE, United Kingdom.
authors.forename: Melissa
authors.initials: M
authors.lastname: Bevan
authors.affiliation: Department of Life Sciences, University of Roehampton, London SW15 4JD.
authors.forename: Meghan
authors.initials: M
authors.lastname: Meintel
authors.affiliation: Pharmacology & Cell Physiology, Division of Biomedical Science, St George's, University of London, London SW17 0RE, United Kingdom. Electronic address: cdavidso@sgul.ac.uk.
authors.forename: Colin
authors.initials: C
authors.lastname: Davidson
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D016642:Bupropion / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000031:analogs & derivatives / Q000494:pharmacology; D004053:Diethylpropion / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D007457:Iodine Radioisotopes; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008839:Microelectrodes; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000502:physiology; D011427:Propiophenones / Q000494:pharmacology; D011869:Radioligand Assay; D017208:Rats, Wistar; D046509:Tissue Culture Techniques
chemical_list: D000662:Amphetamines; D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D011427:Propiophenones; D016642:Bupropion; C079213:RTI 121; D008694:Methamphetamine; C548233:mephedrone; D000661:Amphetamine; C572237:2-ethylamino-1-phenyl-propan-1-one; D003042:Cocaine; D004053:Diethylpropion; D004298:Dopamine
keywords: Amphetamine; Bupropion; Cocaine; Diethylpropion; Ethcathinone; Voltammetry