Investigation of cerebral perfusion changes following MDMA Ecstasy administration in an animal model using bolus-tracking arterial spin labelling MRI

Abstract

The recreational drug of abuse 3,4 methylenedioxymethamphetamine (MDMA; Ecstasy) carries a risk of cerebrovascular accidents (CVA) that may relate to the role of serotonin (5- HT) and/or dopamine in the regulation of cerebrovascular tone. Recent advances in magnetic resonance imaging (MRI) have enabled measurement of cerebral blood perfusion using contrast agent-free approaches such as bolus-tracking arterial spin labeling (btASL). This investigation assessed changes in cerebral perfusion following systemic MDMA administration to rats using btASL MRI. Adult male Wistar rats were administered MDMA (5 or 20 mg/kg; i.p.) or saline, anaesthetised 1, 3 or 24 hours later and a high resolution anatomical scan followed by a continuous ASL (cASL) sequence was conducted using a 7 Tesla MRI scanner. Perfusion-weighted images were generated by subtraction of labelled from control images and experimental data was fitted to a quantitative model of cerebral perfusion to generate mean transit time (MTT), capillary transit time (CTT) and signal amplitude. MTT and CTT are inversely proportional to cerebral blood flow (CBF) and CBF squared respectively, and signal amplitude is proportional to cerebral blood volume (CBV). MDMA induced a reduction in MTT and CTT and an increase in signal amplitude in primary motor, secondary motor and somatosensory cortex I and 3 hours following administration. Such effects were not obtained in sub-cortical regions. The acute effects of MDMA on cerebral perfusion may go some way towards providing a mechanism to explain the occurrence of CVA in vulnerable recreational ecstasy users.