title: Contribution of serotonin and dopamine to changes in core body temperature and locomotor activity in rats following repeated administration of mephedrone.
abstract: The psychoactive effects of mephedrone are commonly compared with those of 3,4-methylenedioxymethamphetamine, but because of a shorter duration of action, users often employ repeated administration to maintain its psychoactive effects. This study examined the effects of repeated mephedrone administration on locomotor activity, body temperature and striatal dopamine and 5-hydroxytryptamine (5-HT) levels and the role of dopaminergic and serotonergic neurons in these responses. Adult male Lister hooded rats received three injections of vehicle (1 ml/kg, i.p.) or mephedrone HCl (10 mg/kg) at 2 h intervals for radiotelemetry (temperature and activity) or microdialysis (dopamine and 5-HT) measurements. Intracerebroventricular pre-treatment (21 to 28 days earlier) with 5,7-dihydroxytryptamine (150 µg) or 6-hydroxydopamine (300 µg) was used to examine the impact of 5-HT or dopamine depletion on mephedrone-induced changes in temperature and activity. A final study examined the influence of i.p. pre-treatment (-30 min) with the 5-HT1Areceptor antagonist WAY-100635 (0.5 mg/kg), 5-HT1Breceptor antagonist GR 127935 (3 mg/kg) or the 5-HT7receptor antagonist SB-258719 (10 mg/kg) on mephedrone-induced changes in locomotor activity and rectal temperature. Mephedrone caused rapid-onset hyperactivity, hypothermia (attenuated on repeat dosing) and increased striatal dopamine and 5-HT release following each injection. Mephedrone-induced hyperactivity was attenuated by 5-HT depletion and 5-HT1Breceptor antagonism, whereas the hypothermia was completely abolished by 5-HT depletion and lessened by 5-HT1Areceptor antagonism. These findings suggest that stimulation of central 5-HT release and/or inhibition of 5-HT reuptake play a pivotal role in both the hyperlocomotor and hypothermic effects of mephedrone, which are mediated in part via 5-HT1Band 5-HT1Areceptors.
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of 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, UK.
authors.forename: Clare H
authors.initials: CH
authors.lastname: Spicer
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, UK.
authors.forename: Francis J P
authors.initials: FJ
authors.lastname: Ebling
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of 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, UK.
authors.forename: Kevin C F
authors.initials: KC
authors.lastname: Fone
authors.affiliation: School of Life Sciences, Medical School, Queen's Medical Centre, The University of Nottingham, UK. madeleine.king@nottingham.ac.uk.
authors.forename: Madeleine V
authors.initials: MV
authors.lastname: King
mesh_terms: D015116:5,7-Dihydroxytryptamine; D018663:Adrenergic Agents / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D006948:Hyperkinesis / Q000139:chemically induced; D007035:Hypothermia / Q000139:chemically induced; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism / Q000502:physiology; D018490:Serotonin Agents / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D018663:Adrenergic Agents; D015259:Dopamine Agents; D009498:Neurotoxins; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D008694:Methamphetamine; C548233:mephedrone; D016627:Oxidopamine; D004298:Dopamine
keywords: 5-HT; dopamine; locomotor activity; mephedrone; microdialysis; telemetry