MDMA 'ecstasy' increases cerebral cortical perfusion determined by bolus‐tracking arterial spin labelling (btASL) MRI. (12th June 2013)

• Record Type: Journal Article
• Authors: Rouine, J; Gobbo, O L; Campbell, M; Gigliucci, V; Ogden, I; McHugh Smith, K; Duffy, P; Behan, B; Byrne, D; Kelly, M E; Blau, C W; Kerskens, C M; Harkin, A
• Is Part Of: British journal of pharmacology. Volume 169:Number 5(2013:Jul.)
• Page Start: 974
• Page End: 987
• Publication Date: 2013-06-12
• Subjects: Pharmacology -- Periodicals; Chemotherapy -- Periodicals; Drug Therapy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/bph.12178
• Languages: English
• ISSNs: 0007-1188

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bph12178-sec-0001" sec-type="section"> <title>Background and Purpose</title> <p>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.</p> </sec> <sec id="bph12178-sec-0002" sec-type="section"> <title>Experimental Approach</title> <p>Cerebral perfusion was quantified using bolus‐tracking arterial spin labelling (btASL) MRI. Rats received MDMA (20 mg·kg<sup>−1</sup>; i.p.) and were assessed 1, 3 or 24 h later. Rats received MDMA (5 or 20 mg·kg<sup>−1</sup>; i.p.) and were assessed 3 h later. In addition, rats received MDMA (5 or 10 mg·kg<sup>−1</sup>; 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.</p> </sec> <sec id="bph12178-sec-0003" sec-type="section"> <title>Key Results</title> <p>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<sup>−1</sup>; i.p.) was attenuated in these animals indicating adaptation in response to prior MDMA exposure.</p> </sec> <sec id="bph12178-sec-0004" sec-type="section"> <title>Conclusions and Implications</title> <p>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.</p> </sec> </abstract>