The role of 5-HT in the impairment of thermoregulation observed in rats administered MDMA ('ecstasy') when housed at high ambient temperature.
BACKGROUND
Administration to rats of a neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) produces an impairment in thermoregulation which is reflected in a prolonged hyperthermic response to a subsequent dose of MDMA given to rats housed at high ambient temperature.


OBJECTIVE
We wished to examine whether the impaired thermoregulation was associated with decreased cerebral 5-HT content produced by the prior neurotoxic dose of MDMA.


METHODS
Rats were injected with drugs decreasing 5-HT function [the tryptophan hydroxlase inhibitor p-chlorophenylalanine (PCPA), and 5-HT receptor antagonists] and rectal temperature was measured after administering MDMA to rats housed at 30 degrees C.


RESULTS
PCPA pretreatment decreased 5-HT and 5-HIAA concentrations in cortex, hippocampus and striatum by >80% and prolonged the hyperthermia induced in rats housed at 30 degrees C by administering MDMA (5 mg/kg i.p.). A similar prolongation of the hyperthermic response to MDMA was seen when rats were pretreated with methysergide (10 mg/kg i.p.) or the 5-HT(1A) antagonist WAY100635 (0.5 mg/kg s.c.).


CONCLUSIONS
Decreasing 5-HT function in diverse ways enhanced the hyperthermic response to MDMA given to rats housed at high ambient temperature. This suggests that loss of 5-HT acting on 5-HT(1A) receptors leads to impaired thermoregulation in rats and suggests that the impairment seen in MDMA pretreated rats housed at high ambient temperature is due to a loss in 5-HT function. These data could have implications for recreational users of MDMA, who may have damaged serotoninergic neurons because of prior heavy or frequent use of the drug, when taking further doses of MDMA in hot environments such as dance clubs.
Saadat
Kathryn S
KS
Neuropharmacology Research Group, Leicester School of Pharmacy, De Montfort University, The Gateway Leicester, LE1 9BH, UK.
O'shea
Esther
E
Colado
M Isabel
MI
Elliott
J Martin
JM
Green
A Richard
AR
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001833:Body Temperature Regulation / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D010134:Fenclonine / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced; D006358:Hot Temperature / Q000009:adverse effects*; D006799:Housing, Animal; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D015306:Biogenic Monoamines; D010879:Piperazines; D011725:Pyridines; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D012701:Serotonin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D010134:Fenclonine; D008784:Methysergide