title: Caffeine alters the behavioural and body temperature responses to mephedrone without causing long-term neurotoxicity in rats.
abstract: Administration of caffeine with 3,4-methylenedioxymethamphetamine (MDMA) alters the pharmacological properties of MDMA in rats. The current study examined whether caffeine alters the behavioural and neurochemical effects of mephedrone, which has similar psychoactive effects to MDMA. Rats received either saline, mephedrone (10 mg/kg), caffeine (10 mg/kg) or combined caffeine and mephedrone intraperitoneally twice weekly on consecutive days for three weeks. Locomotor activity (days 1 and 16), novel object discrimination (NOD, day 2), elevated plus maze (EPM) exploration (day 8), rectal temperature changes (day 9) and pre-pulse inhibition (PPI) of acoustic startle response (day 15) were assessed. Seven days after the final injection, brain regions were collected for the measurement of 5-hydroxytryptamine (5-HT), dopamine and their metabolites. Combined caffeine and mephedrone further enhanced the locomotor response observed following either drug administered alone, and converted mephedrone-induced hypothermia to hyperthermia. Co-administration also abolished mephedrone-induced anxiogenic response on the EPM, but had no effect on NOD or PPI. Importantly, no long-term neurotoxicity was detected following repeated mephedrone alone or when co-administered with caffeine. In conclusion, the study suggests a potentially dangerous effect of concomitant caffeine and mephedrone, and highlights the importance of taking polydrug use into consideration when investigating the acute adverse effect profile of popular recreational drugs.
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham, UK.
authors.forename: Sinead E
authors.initials: SE
authors.lastname: Shortall
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham, UK.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Green
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham, UK.
authors.forename: Kevin Cf
authors.initials: KC
authors.lastname: Fone
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, Nottingham, UK madeleine.king@nottingham.ac.uk.
authors.forename: Madeleine V
authors.initials: MV
authors.lastname: King
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage*; D004192:Discrimination, Psychological / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism; D007035:Hypothermia / Q000139:chemically induced / Q000378:metabolism; D013287:Illicit Drugs / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000209:etiology*; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism
chemical_list: D013287:Illicit Drugs; D012701:Serotonin; D002110:Caffeine; D008694:Methamphetamine; C548233:mephedrone; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine
keywords: Mephedrone; anxiety; body temperature; caffeine; locomotor activity