PMID- 17702902
OWN - NLM
STAT- MEDLINE
DCOM- 20071206
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 323
IP  - 2
DP  - 2007 Nov
TI  - 3,4-Methylenedioxymethamphetamine- and 
      8-hydroxy-2-di-n-propylamino-tetralin-induced hypothermia: role and location of 
      5-hydroxytryptamine 1A receptors.
PG  - 477-87
AB  - The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has complex 
      interactions with thermoregulatory systems, resulting in either hyperthermia or 
      hypothermia. MDMA induces hypothermia when given to animals housed at a low 
      ambient temperature. In this study we report that MDMA (7.5 mg/kg i.p.) given at 
      normal ambient temperatures of 24 to 25 degrees C caused, in conscious freely 
      moving rats, hypothermia (mean decrease from baseline of 1.1 +/- 0.06 degrees C 
      at 40 min). Pretreating animals with a 0.5 mg/kg i.p. dose of the 
      5-hydroxytryptamine 1A (5-HT(1A)) antagonist 
      N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide 
      (WAY 100635) not only prevented MDMA-induced hypothermia, but resulted in the 
      development of hyperthermia (mean temperature increase from baseline of 0.74 +/- 
      0.2 degrees C at 120 min). After treatment with WAY 100635, MDMA also elicited an 
      enhanced tachycardia (mean increases in heart rate from baseline of 110 +/- 16 
      beats/min at 90 min). To identify the location of 5-HT(1A) receptors responsible 
      for hypothermia induced by MDMA, we first investigated the role of 5-HT(1A) 
      receptors in the rostral raphe pallidus (rRP) in decreases in temperature evoked 
      by the known 5-HT(1A) agonist 8-hydroxy-2-di-n-propylamino-tetralin (DPAT). 
      Microinjections of 0.5 nmol of WAY 100635 into the rRP significantly attenuated 
      DPAT (0.2 mg/kg i.p.)-elicited hypothermia. In parallel experiments, we found 
      that microinjections of WAY 100635 into the rRP, while significantly augmenting 
      MDMA-mediated tachycardia, did not alter body temperature. These results 
      demonstrate that although hypothermia mediated by both MDMA and DPAT shares a 
      common dependence on the activation of 5-HT(1A) receptors, the location of these 
      receptors is different for each drug.
FAU - Rusyniak, Daniel E
AU  - Rusyniak DE
AD  - Departments of Emergency Medicine, Indiana University School of Medicine, 
      Indianapolis, Indiana, USA. drusynia@iupui.edu
FAU - Zaretskaia, Maria V
AU  - Zaretskaia MV
FAU - Zaretsky, Dmitry V
AU  - Zaretsky DV
FAU - DiMicco, Joseph A
AU  - DiMicco JA
LA  - eng
GR  - DA20484/DA/NIDA NIH HHS/United States
GR  - NS19883/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070816
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Piperazines)
RN  - 0 (Pyridines)
RN  - 112692-38-3 (Receptor, Serotonin, 5-HT1A)
RN  - 71IH826FEG 
      (N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide)
RN  - 78950-78-4 (8-Hydroxy-2-(di-n-propylamino)tetralin)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - 8-Hydroxy-2-(di-n-propylamino)tetralin/analysis/*pharmacology
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Body Temperature/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Heart Rate/drug effects
MH  - Male
MH  - Motor Activity/drug effects
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Piperazines/pharmacology
MH  - Pyridines/pharmacology
MH  - Raphe Nuclei/drug effects/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Serotonin, 5-HT1A/*physiology
EDAT- 2007/08/19 09:00
MHDA- 2007/12/07 09:00
CRDT- 2007/08/19 09:00
PHST- 2007/08/19 09:00 [pubmed]
PHST- 2007/12/07 09:00 [medline]
PHST- 2007/08/19 09:00 [entrez]
AID - jpet.107.126169 [pii]
AID - 10.1124/jpet.107.126169 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2007 Nov;323(2):477-87. doi: 10.1124/jpet.107.126169. Epub 
      2007 Aug 16.