title: Pre-treatment with 3,4-methylenedioxymethamphetamine (MDMA) causes long-lasting changes in 5-HT2A receptor-mediated glucose utilization in the rat brain.
abstract: The current study examined the long-term effect of brief exposure to 3,4-methylenedioxymethamphetamine (MDMA) on local cerebral glucose utilization (LCGU) in specific 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-five days later and 10 min 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 significant hyperthermia compared with saline-treated controls (p < 0.05-0.01). Eight weeks later, immediately following DOI challenge, LCGU was significantly 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 27-41%), but these did not reach significance. Blood glucose levels were significantly elevated in both groups of DOI-treated rats (p < 0.05-0.01). 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 specific changes in synaptic plasticity.
authors.affiliation: Institute of Neuroscience, Queen's Medical Centre, University of Nottingham, UK.
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Bull
authors.forename: Veronica
authors.initials: V
authors.lastname: Porkess
authors.forename: Michael
authors.initials: M
authors.lastname: Rigby
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hutson
authors.forename: Kevin C F
authors.initials: KC
authors.lastname: Fone
mesh_terms: D000818:Animals; D001345:Autoradiography; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D003847:Deoxyglucose / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects*; D006213:Hallucinogens / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D009714:Nucleus Accumbens / Q000187:drug effects; D011292:Premedication; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D018490:Serotonin Agents / Q000633:toxicity*
chemical_list: D001786:Blood Glucose; D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D018490:Serotonin Agents; D003847:Deoxyglucose; D018817:N-Methyl-3,4-methylenedioxyamphetamine