PMID- 7531765
OWN - NLM
STAT- MEDLINE
DCOM- 19950315
LR  - 20141120
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 272
IP  - 2
DP  - 1995 Feb
TI  - Role of hypothermia in the mechanism of protection against serotonergic toxicity. 
      I. Experiments using 3,4-methylenedioxymethamphetamine, dizocilpine, CGS 19755 
      and NBQX.
PG  - 860-7
AB  - High doses of 3,4-methylenedioxymethamphetamine (MDMA) have been shown to cause 
      long-lasting depletions of central serotonin (5-HT) which are indicative of 
      neuronal toxicity. The noncompetitive N-methyl-D-aspartate (NMDA) receptor 
      antagonist dizocilpine (DZ) attenuates depletions of 5-HT induced by MDMA. 
      Because DZ has been shown to induce hypothermia in rat models of ischemia, the 
      purpose of this study was to assess whether DZ and two other glutamate 
      antagonists, CGS 19755 (CGS) and 
      2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), protect against 
      MDMA-induced 5-HT depletions by induction of hypothermia. Male Sprague-Dawley 
      rats were injected with either saline (SAL), DZ (2.5 mg/kg), CGS (25.0 or 50.0 
      mg/kg x 2 injections) or NBQX (30.0 mg/kg x 2 injections or 55.0 mg/kg x 3 
      injections) followed by either MDMA (40.0 mg/kg) or SAL. Core body temperature 
      (TEMP) was monitored for 4 h or longer using radiotelemetry. Base-line TEMP was 
      between 37.0 and 37.6 degrees C. Administration of DZ with MDMA decreased TEMP to 
      34.0 +/- 0.39 degrees C within 2 h of the MDMA injection, and also protected 
      against serotonergic toxicity. Neither SAL/MDMA nor DZ/SAL had an effect on TEMP 
      over the same period. When rats were treated with DZ/MDMA and TEMP was maintained 
      between 38.4 degrees C and 40.4 degrees C for 4 h, protection against 5-HT 
      depletion was abolished. Coadministration of the competitive NMDA antagonist CGS 
      with MDMA-resulted in a decrease in TEMP to 34.5 +/- 0.27 degrees C, and provided 
      partial protection against 5-HT depletions.(ABSTRACT TRUNCATED AT 250 WORDS)
FAU - Farfel, G M
AU  - Farfel GM
AD  - University of Chicago, Department of Pharmacological and Physiological Sciences, 
      IL 60637.
FAU - Seiden, L S
AU  - Seiden LS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Pipecolic Acids)
RN  - 0 (Quinoxalines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline)
RN  - 333DO1RDJY (Serotonin)
RN  - 4VGJ4A41L2 (selfotel)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Body Temperature/*drug effects
MH  - Brain Chemistry/drug effects
MH  - Dizocilpine Maleate/*pharmacology
MH  - Hydroxyindoleacetic Acid/analysis
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*toxicity
MH  - Pipecolic Acids/*pharmacology
MH  - Quinoxalines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
MH  - Serotonin/*analysis
EDAT- 1995/02/01 00:00
MHDA- 1995/02/01 00:01
CRDT- 1995/02/01 00:00
PHST- 1995/02/01 00:00 [pubmed]
PHST- 1995/02/01 00:01 [medline]
PHST- 1995/02/01 00:00 [entrez]
PST - ppublish
SO  - J Pharmacol Exp Ther. 1995 Feb;272(2):860-7.