Studies on the effect of MDMA ('ecstasy') on the body temperature of rats housed at different ambient room temperatures.
3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') administration to rats produces hyperthermia if they are housed in normal or warm ambient room temperature (Ta) conditions (>or=20 degrees C), but hypothermia when in cool conditions (Ta<or=17 degrees C). We have now investigated some of the mechanisms involved. MDMA (5 mg kg(-1) i.p.) produced a rapid decrease in rectal temperature in rats at Ta 15 degrees C. This response was blocked by pretreatment with the dopamine D2 receptor antagonist remoxipride (10 mg kg(-1) i.p.), but unaltered by pretreatment with the D1 antagonist SCH23390 (1.1 mg kg(-1) i.p). MDMA (5 mg kg(-1)) did not alter the tail temperature of rats at Ta 15 degrees C, but decreased the tail temperature of rats at Ta 30 degrees C. A neurotoxic dose of MDMA (three doses of 5 mg kg(-1) given 3 h apart) decreased cortical and hippocampal 5-HT content by approximately 30% 7 days later. This lesion did not influence the rise in tail temperature when rats were moved from Ta 20 degrees C to 30 degrees C compared to nonlesioned controls, but did result in a lower tail temperature than that of controls when they were returned to Ta 24 degrees C. Acute administration of MDMA (5 mg kg(-1)) to MDMA-lesioned rats produced a sustained decrease in tail temperature in rats housed at Ta 30 degrees C compared to nonlesioned controls. These data suggest that the thermoregulatory problems previously observed in MDMA-lesioned rats housed at Ta 30 degrees C result, partially, from their inability to lose heat by vasodilation of the tail, a major heat-loss organ in this species.
Neuropharmacology Research Group, Leicester School of Pharmacy, De Montfort University, Leicester LE1 9BH. Richard.green@astrazeneca.com
A Richard
AR
Green
Esther
E
O'Shea
Kathryn S
KS
Saadat
J Martin
JM
Elliott
M Isabel
MI
Colado
D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D006213:Hallucinogens / Q000494:pharmacology*; D007035:Hypothermia / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000503:physiopathology; D009498:Neurotoxins / Q000494:pharmacology*; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D013623:Tail / Q000098:blood supply; D013696:Temperature; D014664:Vasodilation / Q000187:drug effects
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D006213:Hallucinogens; D009498:Neurotoxins; D017447:Receptors, Dopamine D1; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine