title: MDMA 'ecstasy' increases cerebral cortical perfusion determined by bolus-tracking arterial spin labelling (btASL) MRI.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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
  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.
authors.affiliation: Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: J
authors.initials: J
authors.lastname: Rouine
authors.forename: O L
authors.initials: OL
authors.lastname: Gobbo
authors.forename: M
authors.initials: M
authors.lastname: Campbell
authors.forename: V
authors.initials: V
authors.lastname: Gigliucci
authors.forename: I
authors.initials: I
authors.lastname: Ogden
authors.forename: K
authors.initials: K
authors.lastname: McHugh Smith
authors.forename: P
authors.initials: P
authors.lastname: Duffy
authors.forename: B
authors.initials: B
authors.lastname: Behan
authors.forename: D
authors.initials: D
authors.lastname: Byrne
authors.forename: M E
authors.initials: ME
authors.lastname: Kelly
authors.forename: C W
authors.initials: CW
authors.lastname: Blau
authors.forename: C M
authors.initials: CM
authors.lastname: Kerskens
authors.forename: A
authors.initials: A
authors.lastname: Harkin
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D006213:Hallucinogens / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D013113:Spin Labels
chemical_list: D006213:Hallucinogens; D018490:Serotonin Agents; D013113:Spin Labels; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine