Brain hyperthermia induced by MDMA (ecstasy): modulation by environmental conditions.
Drugs of abuse, such as 3,4-methylenedioxymethamphetamine (MDMA), often have more powerful effects during states of increased activation and under specific environmental conditions. Because hyperthermia is a major complication of MDMA use and a factor potentiating neurotoxicity, we examined the effects of this drug (9 mg/kg, sc; approximately one-fifth of the known LD(50) in rats) on brain [nucleus accumbens (Nacc) and hippocampus (Hippo)] and muscle (musculus temporalis) temperatures in male rats under conditions that either model human drug use (social interaction with female, warm temperature) or restrict heat dissipation from the brain (chronic occlusion of jugular veins). Under quiet resting conditions at 23 degrees C, MDMA induced a moderate but prolonged hyperthermia. Both NAcc and Hippo showed more rapid and stronger temperature increases than muscle, suggesting metabolic neural activation as a primary cause of brain hyperthermia. During social interaction with a female, brain hyperthermia induced by MDMA was significantly potentiated (+89%). Brain hyperthermia induced by MDMA was also strongly potentiated (+188%) in animals with chronically occluded jugular veins, suggesting impaired cerebral outflow enhances intrabrain heat accumulation. At 29 degrees C, MDMA pushed temperatures in the brain to its biological limits (>41 degrees C; +268%), resulting in fatalities in most (83%) tested animals. Therefore, by inducing metabolic brain activation and restricting heat dissipation, MDMA use under 'party' conditions may be much more dangerous than under standard laboratory conditions.
Brown
P Leon
PL
Behavioural Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Department of Health and Human Services, 5500 Nathan Shock Drive, Baltimore, Maryland 21224, USA.
Kiyatkin
Eugene A
EA
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000503:physiopathology*; D004777:Environment; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D006213:Hallucinogens / Q000009:adverse effects*; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D007398:Interpersonal Relations; D007601:Jugular Veins / Q000294:innervation / Q000503:physiopathology; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000503:physiopathology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D020318:Rats, Long-Evans
D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine