Distribution of temperature changes and neurovascular coupling in rat brain following 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") exposure.
(+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is an abused psychostimulant that produces strong monoaminergic stimulation and whole-body hyperthermia. MDMA-induced thermogenesis involves activation of uncoupling proteins (UCPs), primarily a type specific to skeletal muscle (UCP-3) and absent from the brain, although other UCP types are expressed in the brain (e.g. thalamus) and might contribute to thermogenesis. Since neuroimaging of brain temperature could provide insights into MDMA action, we measured spatial distributions of systemically administered MDMA-induced temperature changes and dynamics in rat cortex and subcortex using a novel magnetic resonance method, Biosensor Imaging of Redundant Deviation in Shifts (BIRDS), with an exogenous temperature-sensitive probe (thulium ion and macrocyclic chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethyl-1,4,7,10-tetraacetate (DOTMA(4-))). The MDMA-induced temperature rise was greater in the cortex than in the subcortex (1.6 ± 0.4 °C versus 1.3 ± 0.4 °C) and occurred more rapidly (2.0 ± 0.2 °C/h versus 1.5 ± 0.2 °C/h). MDMA-induced temperature changes and dynamics in the cortex and body were correlated, although the body temperature exceeded the cortex temperature before and after MDMA. Temperature, neuronal activity, and blood flow (CBF) were measured simultaneously in the cortex and subcortex (i.e. thalamus) to investigate possible differences of MDMA-induced warming across brain regions. MDMA-induced warming correlated with increases in neuronal activity and blood flow in the cortex, suggesting that the normal neurovascular response to increased neural activity was maintained. In contrast to the cortex, a biphasic relationship was seen in the subcortex (i.e. thalamus), with a decline in CBF as temperature and neural activity rose, transitioning to a rise in CBF for temperature above 37 °C, suggesting that MDMA affected CBF and neurovascular coupling differently in subcortical regions. Considering that MDMA effects on CBF and heat dissipation (as well as potential heat generation) may vary regionally, neuroprotection may require different cooling strategies.
Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA.|Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, USA.|Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Daniel
D
Coman
Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA.|Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, USA.|Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Basavaraju G
BG
Sanganahalli
Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA.|Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.
Lihong
L
Jiang
Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA.|Core Center for Quantitative Neuroscience with Magnetic Resonance (QNMR), Yale University, New Haven, CT, USA.|Department of Diagnostic Radiology, Yale University, New Haven, CT, USA.|Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Fahmeed
F
Hyder
Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT, USA.|Department of Psychiatry, Yale University, New Haven, CT, USA.
Kevin L
KL
Behar
D000768:Anesthesia, General; D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000098:blood supply / Q000187:drug effects*; D002540:Cerebral Cortex / Q000098:blood supply / Q000187:drug effects; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D000069336:Neurovascular Coupling / Q000187:drug effects*; D009942:Organometallic Compounds / Q000032:analysis / Q000493:pharmacokinetics; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000098:blood supply / Q000187:drug effects
D009942:Organometallic Compounds; C550981:thulium(III) 1,4,7,10-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate; D018817:N-Methyl-3,4-methylenedioxyamphetamine
BIRDS; TmDOTMA; blood flow; ecstasy; heat; oxidative metabolism