ORIGINAL INVESTIGATION Acute concomitant effects of MDMA binge dosing on extracellular 5-HT, locomotion and body temperature and the long-term effect on novel object discrimination in rats Ratchanee Rodsiri & Clare Spicer & A. Richard Green & Charles A. Marsden & Kevin C. F. Fone Received: 10 March 2010 / Accepted: 9 June 2010 / Published online: 20 July 2010 # Springer-Verlag 2010 Abstract Rationale 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) produces an acute release of 5-HT in the brain, together with increased locomotion and hyperthermia. Objective This study examined whether the acute functional changes of locomotor activity and body temperature are related to enhanced 5-HT release induced by MDMA. Methods We concomitantly measured changes in extraneuro- nal 5-HT by in vivo brain microdialysis and used radiote- lemetry to measure locomotion and body temperature to establish whether any positive correlations occur between these three parameters. ‘Binge-type’ repeated administration of low doses of MDMA (3 and 6 mg/kg given at 2-h intervals three times) were given to provide drug exposure similar to that experienced by recreational drug users. Results MDMA induced acute hyperactivity, changes in core body temperature (both hypothermia and hyperthermia) and elevation of hippocampal 5-HT overflow, all of which were dependent on the dose of MDMA administered. The change in locomotor activity and the magnitude of the hyperthermia appeared to be unrelated both to each other and to the magnitude of MDMA-induced 5-HT release. The study also found evidence of long-term disruption of novel object discrimination 2 weeks following “binge-type” repeated MDMA administration. Conclusions MDMA-induced 5-HT release in the brain was not responsible for either the hyperthermia or increased locomotor activity that occurred. Since neither dose schedule of MDMA induced a neurotoxic loss of brain 5-HT 2 weeks after its administration, the impairment of recognition memory found in novel object discrimination probably results from other long-term changes yet to be established. Keywords 3,4-methylenedioxymethamphetamine . 5-HT . Body temperature . Locomotor activity . Novel object discrimination . Radiotelemetry . In vivo microdialysis Introduction Over the last decade, the pattern of 3,4-methylenediox- ymethamphetamine (MDMA) ingestion by humans has often involved repeated low-dose drug administration over a single short time period which is referred to as ‘binge use’ (Hammersley et al. 1999; Parrott 2005; Topp et al. 1999; Winstock et al. 2001). It is claimed that binge use of MDMA boosts its subjective effects and sustains the actions of the drug over time (Parrott 2005). The predom- inant acute adverse event following MDMA ingestion is hyperthermia and this can lead to other associated clinical problems, including rhabdomyolysis, intravascular coagu- lation, acute renal failure and even death (see Green et al. 2003). In animal studies, Green et al. (2004) reported a dose-dependent MDMA-induced hyperthermia following repeated MDMA (2, 4 and 6 mg/kg×3 every 3 h) administration to rats and Baumann et al. (2008a) similarly showed a marked and sustained increase of body temper- ature following MDMA (7.5 mg/kg×3 every 2 h). In addition to acute hyperthermia, Kindlundh-Hogberg et al. (2007) reported hyperactivity caused by repeated MDMA (5 mg/kg×3 every 3 h) and showed that this pattern of R. Rodsiri : C. Spicer : A. R. Green : C. A. Marsden : K. C. F. Fone (*) School of Biomedical Sciences, Institute of Neuroscience, Medical School, Queen’s Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK e-mail: kevin.fone@nottingham.ac.uk Psychopharmacology (2011) 213:365–376 DOI 10.1007/s00213-010-1921-9