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Published on: May 12, 2018
MDMA-evoked changes in cerebral blood flow in living porcine brain: correlation with hyperthermia
Pedro Rosa-Neto1, Aage K Olsen, Albert Gjedde
1Center for Functionally Integrative Neuroscience, Aarhus University and PET Center, Aarhus University Hospitals, Aarhus C, 8000, Denmark. pedro@pet.auh.dk
Abstract:
3,4-Methylenedioxymethamphetamine (MDMA) acutely releases intraneuronal dopamine and serotonin and evokes hyperthermia which is linked to toxicity for serotonin fibers. The acute effects of MDMA on cerebral blood flow (CBF) in living brain have not been described in an animal model of MDMA intoxication. We predicted that MDMA-induced hyperthermia should correlate with increased CBF in the hypothalamus, a serotonin-rich brain region subserving thermoregulation. To test this prediction, we used positron emission tomography with statistical parametric mapping for exploratory analysis of the focal changes in the magnitude of CBF in the anesthetized female Landrace pig (n = 9) at 30 and 150 min after acute challenge with MDMA-HCl (1 mg/kg, i.v.). The MDMA treatment was followed by increased CBF in the occipital cortex and in the medial mesencephalon overlapping the dorsal raphé nucleus, and reduced CBF in the cerebellar vermis and in a cluster in the medulla encompassing the left locus coeruleus. The individual increase of body temperature correlated positively with increased CBF in the vicinity of the raphé nucleus, in the hypothalamus (regions linked to thermoregulation), and also in the medial frontal cortex, which together comprise the regions receiving the most dense serotonin innervations in pig brain. Thus, individual differences in the susceptibility to MDMA-induced hyperthermia in this population correlated with the magnitude of focal increases in CBF within specific brain regions endowed with a dense serotonin innervation, including regions linked to thermoregulation.
Insights
3,4-Methylenedioxymethamphetamine (MDMA) increases cerebral blood flow (CBF) in specific brain regions, particularly those rich in serotonin. This blood flow increase correlates with MDMA-induced hyperthermia and may indicate susceptibility to its toxic effects.
Area of Science:
- Neuroscience
- Pharmacology
- Medical Imaging
Background:
- 3,4-Methylenedioxymethamphetamine (MDMA) releases dopamine and serotonin, causing hyperthermia linked to serotonin fiber toxicity.
- The acute effects of MDMA on cerebral blood flow (CBF) in a living animal model are not well-described.
- Hyperthermia from MDMA is hypothesized to correlate with increased CBF in thermoregulatory regions like the hypothalamus.
Purpose of the Study:
- To investigate the acute effects of MDMA on CBF in the brain using an animal model.
- To determine if MDMA-induced hyperthermia correlates with focal changes in CBF in specific brain regions.
Main Methods:
- Positron emission tomography (PET) with statistical parametric mapping was used to analyze focal CBF changes.
- Anesthetized female Landrace pigs (n=9) received an acute intravenous challenge with MDMA-HCl (1 mg/kg).
- CBF was measured at 30 and 150 minutes post-MDMA administration.
Main Results:
- MDMA increased CBF in the occipital cortex and medial mesencephalon (overlapping the dorsal raphe nucleus).
- Reduced CBF was observed in the cerebellar vermis and the left locus coeruleus.
- Increased body temperature positively correlated with increased CBF in the hypothalamus, raphe nucleus vicinity, and medial frontal cortex.
Conclusions:
- Individual susceptibility to MDMA-induced hyperthermia correlates with the magnitude of focal CBF increases in serotonin-rich brain regions.
- These findings highlight the relationship between MDMA's effects on CBF, thermoregulation, and serotonin pathways.
- The study provides novel insights into the neurovascular effects of MDMA in a mammalian model.
