MDMA 'ecstasy' increases cerebral cortical perfusion determined by bolus-tracking arterial spin labelling (btASL) MRI
J Rouine1, O L Gobbo, M Campbell
1Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
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.
Insights
3,4-methylendioxymethamphetamine (MDMA) acutely increases cerebral perfusion in rats, evidenced by reduced transit times. However, long-term MDMA exposure does not sustain these perfusion changes and attenuates the acute response.
Area of Science:
- Neuroscience
- Pharmacology
- Medical Imaging
Background:
- Recreational drug use, including 3,4-methylendioxymethamphetamine (MDMA), poses risks to brain health.
- Understanding the neurovascular effects of MDMA is crucial for assessing its potential long-term consequences.
Purpose of the Study:
- To investigate the impact of systemic MDMA administration on cerebral perfusion in a rat model.
- To quantify changes in cerebral blood flow dynamics using advanced neuroimaging techniques.
Main Methods:
- Bolus-tracking arterial spin labelling (btASL) MRI at 7 Tesla was employed to measure cerebral perfusion.
- Rats received varying doses of MDMA acutely or repeatedly over two days.
- Quantitative parameters including mean transit time (MTT) and capillary transit time (CTT) were derived.
Main Results:
- Acute MDMA administration (20 mg·kg(-1)) led to decreased MTT and CTT, indicating increased cortical perfusion.
- Repeated MDMA exposure resulted in long-term reductions in cortical serotonin (5-HT) but did not cause sustained perfusion alterations.
- Prior MDMA exposure attenuated the acute perfusion response, suggesting adaptive mechanisms.
Conclusions:
- MDMA induces quantifiable changes in cortical perfusion, measurable by btASL MRI.
- btASL MRI demonstrates translational potential for studying drug-induced cerebrovascular effects.
- Further research is needed to explore the mechanisms underlying these changes and their behavioral correlates.
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