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Pre-treatment with 3,4-methylenedioxymethamphetamine (MDMA) causes long-lasting changes in 5-HT2A receptor-mediated glucose utilization in the rat brain

Institute of Neuroscience, Queen's Medical Centre, University of Nottingham, Nottingham, UK

Veronica Porkess

Michael Rigby

Peter H. Hutson

Merck Sharp and Dohme Neuroscience Research Centre, Harlow, Essex, UK

Kevin C. F. Fone

Institute of Neuroscience, Queen's Medical Centre, University of Nottingham, Nottingham, UK

The current study examined the long-term effect of brief exposure to 3,4-methylenedioxymethamphetamine (MDMA) on local cerebral glucose utilization (LCGU) in speci.c brain regions immediately following administration of the 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Wistar rats (post-natal day (PND) 28, n= 24) were administered MDMA (5 mg/kg, i.p.) or saline (1 ml/kg, i.p.) four times daily for 2 consecutive days and core body temperature was recorded. Fifty-.ve days later and 10min following injection of DOI (1 mg/kg, i.p.) or saline, LCGU was measured using the [14C]2-deoxyglucose (2-DG) technique. In the 4 hours following the initial injection (PND 28), MDMA-treated rats exhibited signi.cant hyperthermia compared with saline-treated controls (p< 0.05ñ0.01). Eight weeks later, immediately following DOI challenge, LCGU was signi.cantly elevated (an increase of 47%, p< 0.05) in the nucleus accumbens of MDMA/DOI pretreated rats, compared with that in MDMA/saline pre-treated controls. A similar trend was observed in other areas such as the lateral habenula, somatosensory cortex and hippocampal regions (percentage changes of 27ñ41%), but these did not reach signi.cance. Blood glucose levels were signi.cantly elevated in both groups of DOI-treated rats (p< 0.05ñ0.01). Thus, brief exposure of young rats to an MDMA regimen previously shown to cause anxiety-like behaviour and modest serotonergic neurotoxicity (Bull et al., 2004) increased DOI-induced energy metabolism in the nucleus accumbens and tended to increase metabolism in other brain regions, including the hippocampus, consistent with the induction of long-term brain region speci.c changes in synaptic plasticity.

Key Words: [14C]2-deoxyglucose autoradiography • 5-hydroxytryptamine (5-HT, serotonin) • 5-HT2A receptor • local cerebral glucose utilization (LCGU) • 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) • nucleus accumbens

Journal of Psychopharmacology, Vol. 20, No. 2, 272-280 (2006)
DOI: 10.1177/0269881106059583


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