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 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.