PMID- 19121330
OWN - NLM
STAT- MEDLINE
DCOM- 20090306
LR  - 20211020
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 235
IP  - 1
DP  - 2009 Feb 15
TI  - The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is 
      sensitive to sex differences.
PG  - 33-8
LID - 10.1016/j.taap.2008.12.003 [doi]
AB  - Female subjects have been reported to be less sensitive to the hyperthermic 
      effects of 3,4-methylenedioxymethamine (MDMA) than males. Studies were designed 
      to examine the cellular mechanisms involved in these sex sensitive differences. 
      Gonadectomized female and male rats were treated with a 200 microg 100 microL(-1) 
      of estrogen or 100 microg 100 microL(-1) of testosterone respectively every 5 
      days for a total of three doses. Rats were then challenged with either saline or 
      MDMA (20 mg kg(-1), sc). Rats were then euthanized and aortas were constricted, 
      in vitro, by serial phenylephrine (Phe) addition with or without the inhibitor of 
      nitric oxide (NO) synthase, g-nitro-L-Arginine-Methyl Ester (L-NAME). Skeletal 
      muscle uncoupling protein-3 (UCP3) expression was measured as well as plasma 
      norepinephrine (NE) levels. All males but no females developed hyperthermia 
      following MDMA treatment. The EC(50) for Phe dose response curves increased only 
      in the females treated with MDMA and T(max) for Phe increased following L-NAME 
      only in the females. Both males and females demonstrated an increase in plasma NE 
      following MDMA treatment; however, males displayed a significantly greater NE 
      concentration. Skeletal muscle UCP3 expression was 80% less in females than in 
      males. These results suggest that the inability of MDMA to induce a thermogenic 
      response in the female subjects may be due to four sex-specific mechanisms: 1) 
      Female subjects have reduced sympathetic activation following MDMA challenge; 2) 
      Female vasculature is less sensitive to alpha(1)-AR stimulation following MDMA 
      challenge; 3) Female vasculature has an increased sensitivity to NO; 4) UCP3 
      expression in skeletal muscle is less in females.
FAU - Wyeth, Richard P
AU  - Wyeth RP
AD  - Division of Pharmacology, Virginia College of Osteopathic Medicine, Blacksburg, 
      VA 24060, USA.
FAU - Mills, Edward M
AU  - Mills EM
FAU - Ullman, Alison
AU  - Ullman A
FAU - Kenaston, M Alexander
AU  - Kenaston MA
FAU - Burwell, Johanna
AU  - Burwell J
FAU - Sprague, Jon E
AU  - Sprague JE
LA  - eng
GR  - R01 DK089224/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081214
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Adrenergic alpha-1 Receptor Agonists)
RN  - 0 (Hallucinogens)
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Ucp3 protein, rat)
RN  - 0 (Uncoupling Protein 3)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic alpha-1 Receptor Agonists
MH  - Animals
MH  - Aorta/drug effects
MH  - Female
MH  - Fever/*chemically induced
MH  - Gene Expression Regulation
MH  - Hallucinogens/*toxicity
MH  - Ion Channels/genetics/metabolism
MH  - Male
MH  - Mitochondrial Proteins/genetics/metabolism
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Nitric Oxide/pharmacology
MH  - Norepinephrine/metabolism
MH  - Rats
MH  - *Sex Characteristics
MH  - Uncoupling Protein 3
EDAT- 2009/01/06 09:00
MHDA- 2009/03/07 09:00
CRDT- 2009/01/06 09:00
PHST- 2008/10/21 00:00 [received]
PHST- 2008/12/01 00:00 [revised]
PHST- 2008/12/04 00:00 [accepted]
PHST- 2009/01/06 09:00 [entrez]
PHST- 2009/01/06 09:00 [pubmed]
PHST- 2009/03/07 09:00 [medline]
AID - S0041-008X(08)00507-3 [pii]
AID - 10.1016/j.taap.2008.12.003 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2009 Feb 15;235(1):33-8. doi: 10.1016/j.taap.2008.12.003. 
      Epub 2008 Dec 14.