Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Neuropsychobiology 2009;60:195–203 DOI: 10.1159/000253555 Weekly -Hydroxybutyrate Exposure Sensitizes Locomotor Hyperactivity to Low-Dose 3,4-Methylenedioxymethamphetamine in Rats P.S. van Nieuwenhuijzen a K.M. Li b G.E. Hunt c I.S. McGregor a a School of Psychology, b Department of Pharmacology and c Department of Psychological Medicine, University of Sydney, Concord Hospital, Sydney, N.S.W., Australia MDMA-induced hyperthermia. After a washout period of 5 weeks, rats pre-exposed to MDMA, GHB and MDMA/GHB showed no hyperactivity when tested drug-free in the con- text in which they had previously received drugs, but dis- played a sensitized locomotor response to a low challenge dose of MDMA (2.5 mg/kg). The response to a low dose of methamphetamine (0.5 mg/kg) did not differ among groups. Neurochemical analysis using high-performance liquid chromatography revealed few lasting changes in serotonin, dopamine or their metabolites in the striatum or prefrontal cortex of MDMA- or GHB-pre-exposed rats. These results in- dicate that GHB modulates the locomotor and hyperthermic response to acute MDMA and that pre-exposure to GHB can sensitize the locomotor response to low doses of MDMA. Copyright © 2009 S. Karger AG, Basel The popular drug 3,4-methylenedioxymethamphet- amine (MDMA, ecstasy) is widely used in many Western countries due to its euphoric and empathogenic proper- ties [1]. By binding to membrane monoamine transport- ers, MDMA elevates the synaptic concentrations of 5-hy- droxytryptamine (5-HT), dopamine (DA) and noradren- aline (NA) [2]. The acute side effects of MDMA include hyperthermia, 5-HT syndrome, cardiac arrhythmias and, in rare circumstances, death [3] . In laboratory ani- Key Words Dopamine  -Hydroxybutyrate  3,4-Methylenedioxymethamphetamine  Polydrug use  Sensitization  5-Hydroxytryptamine Abstract Users of the popular party drug 3,4-methylenedioxymeth- amphetamine (MDMA) sometimes report combining MDMA with -hydroxybutyrate (GHB) to enhance the pleasurable effects of both drugs. However, very few studies have exam- ined the influences of this drug combination. The present study investigated the development of locomotor sensitiza- tion in laboratory rats given 7 once-weekly exposures to ei- ther MDMA, GHB or their combination (MDMA/GHB). The drugs were administered at a high ambient temperature (28 ° C) to mimic nightclub conditions. MDMA (5 mg/kg), giv- en once weekly, produced a progressively greater locomotor and hyperthermic response over time. In contrast, GHB (500 mg/kg) administered weekly produced consistent low levels of locomotor activity and few changes in body temperature. Rats receiving the mixture of MDMA (5 mg/kg) and GHB (500 mg/kg) showed asymptotic levels of sensitized locomotor activity similar to those seen in rats given MDMA alone, but the development of locomotor sensitization was delayed by coadministered GHB. GHB also delayed the development of Published online: November 5, 2009 Prof. I.S. McGregor School of Psychology University of Sydney Sydney, N.S.W. 2006 (Australia) Tel. +61 2 9351 3571, Fax +61 2 9351 8023, E-Mail iain @ psych.usyd.edu.au © 2009 S. Karger AG, Basel 0302–282X/09/0604–0195$26.00/0 Accessible online at: www.karger.com/nps