Treadmill running restores MDMA-mediated hyperthermia prevented by inhibition of the dorsomedial hypothalamus.
The contribution of exercise to hyperthermia mediated by MDMA is not known. We recently showed that inhibiting the dorsomedial hypothalamus (DMH) attenuated spontaneous locomotion and hyperthermia and prevented deaths in rats given MDMA in a warm environment. The goal of this study was to confirm that restoring locomotion through a treadmill would reverse these effects thereby confirming that locomotion mediated by the DMH contributes to MDMA-mediated hyperthermia. Rats were randomized to receive bilateral microinjections, into the region of the DMH, of muscimol (80pmol/100nl) or artificial CSF followed by a systemic dose of either MDMA (7.5mg/kg, i.v.) or saline. Immediately after the systemic injection, rats were placed on a motorized treadmill maintained at 32°C. Rats were exercised at a fixed speed (10m/min) until their core temperature reached 41°C. Our results showed that a fixed exercise load abolished the decreases in temperature and mortality, seen previously with inhibition of the DMH in freely moving rats. Therefore, locomotion mediated by neurons in the DMH is critical to the development of hyperthermia from MDMA.
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Dmitry V
DV
Zaretsky
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Maria V
MV
Zaretskaia
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.
Pamela J
PJ
Durant
Department of Emergency Medicine, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: drusynia@iu.edu.
Daniel E
DE
Rusyniak
D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D005080:Exercise Test / Q000009:adverse effects*; D005334:Fever / Q000209:etiology*; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006213:Hallucinogens / Q000494:pharmacology*; D007033:Hypothalamus, Middle / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013686:Telemetry
D058785:GABA-A Receptor Agonists; D006213:Hallucinogens; D009118:Muscimol; D018817:N-Methyl-3,4-methylenedioxyamphetamine
Dorsomedial hypothalamus; Heat stroke; Hyperthermia; Locomotion; MDMA