Background and purpose: The purpose of this study was to assess cerebral perfusion changes following systemic administration of the recreational drug 3,4-methylendioxymethamphetamine (MDMA 'ecstasy') to rats.
Experimental approach: Cerebral perfusion was quantified using bolus-tracking arterial spin labelling (btASL) MRI. Rats received MDMA (20 mg·kg(-1); i.p.) and were assessed 1, 3 or 24 h later. Rats received MDMA (5 or 20 mg·kg(-1); i.p.) and were assessed 3 h later. In addition, rats received MDMA (5 or 10 mg·kg(-1); i.p.) or saline four times daily over 2 consecutive days and were assessed 8 weeks later. Perfusion-weighted images were generated in a 7 tesla (7T) MRI scanner 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.
Key results: MDMA reduces MTT and CTT and increases amplitude in somatosensory and motor cortex 1 and 3 h following administration, indicative of an increase in perfusion. Prior exposure to MDMA provoked a long-term reduction in cortical 5-HT concentration, but did not produce a sustained effect on cerebral cortical perfusion. The response to acute MDMA challenge (20 mg·kg(-1); i.p.) was attenuated in these animals indicating adaptation in response to prior MDMA exposure.
Conclusions and implications: MDMA provokes changes in cortical perfusion, which are quantifiable by btASL MRI, a neuroimaging tool with translational potential. Future studies are directed towards elucidation of the mechanisms involved and correlating changes in cerebrovascular function with potential behavioural deficits associated with drug use.
© 2013 The Authors. British Journal of Pharmacology © 2013 The British Pharmacological Society.