PMID- 11441431
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20220225
IS  - 0033-3158 (Print)
IS  - 0033-3158 (Linking)
VI  - 155
IP  - 4
DP  - 2001 Jun
TI  - A neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) to rats 
      results in a long-term defect in thermoregulation.
PG  - 413-8
AB  - RATIONALE: 3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") administration to 
      rats produces damage to cerebral 5-HT nerve endings; however, the long-term 
      functional consequences of this damage are poorly understood. OBJECTIVE: To 
      confirm that MDMA administration produces a long-term effect on thermoregulation 
      and investigate the mechanisms involved. METHODS: Male Dark Agouti rats were 
      injected with a neurotoxic dose of MDMA (12.5 mg/kg i.p.). Five to 6 weeks later, 
      they were exposed to high ambient temp (30 degrees C) for 60 min followed by a 
      return to normal temp (20 degrees C), with rectal temperature being measured 
      under both conditions. Further groups of MDMA-pretreated rats were challenged 
      with 8-OH-DPAT and their temperature response measured. RESULTS: MDMA 
      administration produced acute hyperthermia. Rectal temperature had normalised 24 
      h later and was similar to saline-injected controls over the following 15 days. 
      MDMA administration produced a 37% loss in hypothalamic 5-HT content 18 days 
      later. When MDMA-pretreated rats were subjected to high ambient temperature 33 
      days posttreatment, they displayed both a faster rise in rectal temperature and 
      sustained hyperthermia when returned to normal conditions. There was no 
      difference in their hypothermic response to the 5-HT1A agonist 8-OH-DPAT. 
      CONCLUSIONS: A neurotoxic dose of MDMA resulted in impaired thermoregulation when 
      rats were exposed to high ambient temperature. 5-HT1A receptor mechanisms were 
      unaltered. Impaired serotonergic function following MDMA presumably alters the 
      neurotransmitter balance, thereby compromising thermoregulation. Heavy 
      recreational users of MDMA may also have impaired thermoregulation and thus be at 
      greater risk of an acute adverse response to MDMA in a hot crowded dance 
      environment.
FAU - Mechan, A O
AU  - Mechan AO
AD  - Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, De 
      Montfort University, The Gateway, Leicester LE1 9BH, UK.
FAU - O'Shea, E
AU  - O'Shea E
FAU - Elliott, J M
AU  - Elliott JM
FAU - Colado, M I
AU  - Colado MI
FAU - Green, A R
AU  - Green AR
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Psychopharmacology (Berl)
JT  - Psychopharmacology
JID - 7608025
RN  - 0 (Amphetamines)
RN  - 0 (Hallucinogens)
RN  - 0 (Piperazines)
RN  - 0 (Serotonin Receptor Agonists)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - OOM10GW9UE (4-iodo-2,5-dimethoxyphenylisopropylamine)
RN  - REY0CNO998 (1-(3-chlorophenyl)piperazine)
SB  - IM
MH  - Amphetamines/pharmacology
MH  - Animals
MH  - Body Temperature/drug effects
MH  - Body Temperature Regulation/*drug effects
MH  - Brain Chemistry/drug effects
MH  - Hallucinogens/*toxicity
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Neurotoxicity Syndromes/*physiopathology
MH  - Piperazines/pharmacology
MH  - Rats
MH  - Serotonin/metabolism
MH  - Serotonin Receptor Agonists/pharmacology
EDAT- 2001/07/10 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/07/10 10:00
PHST- 2001/07/10 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/07/10 10:00 [entrez]
AID - 10.1007/s002130100735 [doi]
PST - ppublish
SO  - Psychopharmacology (Berl). 2001 Jun;155(4):413-8. doi: 10.1007/s002130100735.