MDMA-evoked changes in cerebral blood flow in living porcine brain: correlation with hyperthermia

Synapse. 2004 Sep 15;53(4):214-21. doi: 10.1002/syn.20052.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Cerebral Arteries / diagnostic imaging
  • Cerebral Arteries / drug effects*
  • Cerebral Arteries / physiology
  • Cerebrovascular Circulation / drug effects*
  • Cerebrovascular Circulation / physiology
  • Disease Models, Animal
  • Female
  • Fever / chemically induced*
  • Fever / physiopathology
  • Hypothalamus / blood supply
  • Hypothalamus / diagnostic imaging
  • Hypothalamus / drug effects
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Prefrontal Cortex / blood supply
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / drug effects
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism
  • Raphe Nuclei / blood supply
  • Raphe Nuclei / diagnostic imaging
  • Raphe Nuclei / drug effects
  • Serotonin / metabolism
  • Sus scrofa / anatomy & histology
  • Sus scrofa / physiology*
  • Tomography, Emission-Computed

Substances

  • Serotonin
  • N-Methyl-3,4-methylenedioxyamphetamine