ORIGINAL INVESTIGATION Serotonin 5-HT4 receptors in the nucleus accumbens are specifically involved in the appetite suppressant and not locomotor stimulant effects of MDMA (‘ecstasy’) H. M. Francis & N. J. Kraushaar & L. R. Hunt & J. L. Cornish Received: 16 December 2009 / Accepted: 8 June 2010 / Published online: 26 August 2010 # Springer-Verlag 2010 Abstract Rationale 3,4-Methylenedioxymethamphetamine (MDMA) abuse is a substantial problem in young adults. Due to a high focus on body image in this population, two main factors that may encourage MDMA use are the appetite suppressant and locomotor stimulant effects of this drug. The nucleus accumbens (NAc) is a brain region associated with the regulation of motivated and locomotor behaviours, and recent evidence suggests that NAc 5-HT4 receptors are likely to be involved in the appetite suppressant effect of MDMA. It has not yet been shown whether 5-HT4 receptors of the NAc are involved in the locomotor stimulant effects of MDMA, which may also contribute to a reduction in food intake. Objectives This study aimed to investigate the effect of local antagonism of serotonin 5-HT4 receptors in the NAc in the appetite suppressant and locomotor stimulant effects of MDMA. Methods Male hooded Wistar rats underwent surgery for the implantation of bilateral NAc microinjection cannulae under isofluorane anesthesia. Following 5–7 days of recovery, the rats received bilateral microinjections of the 5-HT4 antagonist RS39604 into the NAc immediately prior to either saline or MDMA administration. Food intake, water intake, body weight and locomotor activity were measured. Results RS39604 significantly increased food intake and increased weight loss in MDMA-treated but not saline-treated rats. Measures of MDMA-induced water intake or locomotor activity were not altered by antagonist administration. Conclusions These results demonstrate that 5-HT4 receptors in the NAc specifically regulate the appetite suppressant effects of MDMA but not MDMA-induced water intake or locomotor activity. Keywords Ecstacy . Nucleus accumbens . Appetite . Locomotor . Weight loss Abbreviations 5-HT Serotonin MDMA 3,4 Methylenedioxymethamphetamine NAc Nucleus accumbens ip Intraperitoneal Introduction 3,4-Methylenedioxymethamphetamine (MDMA or ‘ecstasy’) use is estimated to affect nine million people in the global population aged 15–64, with considerably high prevalence rates among the 20–29-year-old age group (United Nations Office on Drugs and Crime UNDOC 2008). The increased use of this drug, especially among 20–29 year olds, indicates a need for greater understanding of its effects and the factors motivating its use, as well as a need to develop prevention messages and treatment plans targeted at young adults (Degenhardt et al. 2009). Although MDMA is typically thought to appeal to users due to promoting euphoric and motor stimulant effects, the ages associated with recreational drug use (adolescence and early adulthood) are also associated H. M. Francis : N. J. Kraushaar : L. R. Hunt : J. L. Cornish Neuropharmacology Laboratory, Department of Psychology, Macquarie University, Sydney, Australia J. L. Cornish (*) Department of Psychology, C3A, Macquarie University, North Ryde, New South Wales, Australia 2109 e-mail: jcornish@psy.mq.edu.au Psychopharmacology (2011) 213:355–363 DOI 10.1007/s00213-010-1982-9