title: Comparative pharmacological evaluation of the cathinone derivatives, mephedrone and methedrone, in mice.
abstract: Mephedrone and methedrone are cathinone-related compounds, which act as non-selective substrates for monoamine transporters, facilitating a neurotransmitter release. We compared the acute pharmacological effects of mephedrone and methedrone, attempting to further evaluate the action mechanisms of methedrone by responsibly and ethically using mice under approved procedures. The effects of both compounds were examined from 10 to 60 min, in a series of behavioral paradigms, namely open-field, plus-maze, hot-plate and tail suspension tests, whereas neurotransmitter brain tissue levels were determined ex vivo by HPLC. Separate groups were pre-treated with the dopamine (DA) antagonist haloperidol, or the serotonin (5-HT) synthesis inhibitor ρCPA, to further assess the mechanisms underlying methedrone effects. The compounds caused marked hyperlocomotion, displaying dissimilar stereotyped behavior, in an open-field arena. Mephedrone caused anxiolytic-like effects, while methedrone induced anxiogenic-like actions in the elevated plus-maze. Both compounds displayed thermal antinociception, with a reduced immobility time in the tail suspension model. Mephedrone triggered a 2- and 3-fold increment of dopamine and serotonin tissue levels, respectively, in the nucleus accumbens, with a 1.5-fold elevation of tissue dopamine in the frontal cortex. Methedrone caused a 2-fold increment of tissue dopamine in the nucleus accumbens and in the striatum, and a 1.5-fold increment of serotonin tissue levels in the hippocampus and striatum. In vivo methedrone effects were partially inhibited by a pre-treatment with haloperidol or ρCPA. Despite similar actions on locomotion, analgesia, and depression-like behavior, the acute administration of mephedrone and methedrone elicited divergent effects on anxiety-like behavior and stereotyped movements in mice, which might be related to the distinct modulation of brain tissue neurotransmitter levels.
authors.affiliation: PUCRS, Programa de Pós-graduação em Biologia Celular e Molecular, Porto Alegre, RS, Brazil.
authors.forename: Priscilla B
authors.initials: PB
authors.lastname: Pail
authors.affiliation: PUCRS, Programa de Pós-graduação em Medicina e Ciências da Saúde, Porto Alegre, RS, Brazil.
authors.forename: Kesiane M
authors.initials: KM
authors.lastname: Costa
authors.affiliation: PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre, RS, Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Leite
authors.affiliation: PUCRS, Programa de Pós-graduação em Medicina e Ciências da Saúde, Porto Alegre, RS, Brazil; PUCRS, Instituto de Toxicologia e Farmacologia, Porto Alegre, RS, Brazil; PUCRS, Faculdade de Odontologia, Porto Alegre, RS, Brazil. Electronic address: camposmmartha@yahoo.com.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Campos
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006213:Hallucinogens / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D019417:Hindlimb Suspension; D008124:Locomotion / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018377:Neurotransmitter Agents / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010622:Phencyclidine / Q000494:pharmacology; D011427:Propiophenones / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D014151:Anti-Anxiety Agents; D006213:Hallucinogens; D018377:Neurotransmitter Agents; D011427:Propiophenones; D008694:Methamphetamine; C548233:mephedrone; D010622:Phencyclidine; D006220:Haloperidol; C558328:4-methoxymethcathinone
keywords: Behavior; Cathinone derivatives; Mephedrone; Methedrone; Mice; Tissue neurotransmitters