PMID- 11907167
OWN - NLM
STAT- MEDLINE
DCOM- 20020418
LR  - 20190607
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 301
IP  - 1
DP  - 2002 Apr
TI  - 3,4-Methylenedioxymethamphetamine produces glycogenolysis and increases the 
      extracellular concentration of glucose in the rat brain.
PG  - 138-44
AB  - Oxidative and/or bioenergetic stress is thought to contribute to the mechanism of 
      neurotoxicity of amphetamine derivatives, e.g., 3,4-methylenedioxymethamphetamine 
      (MDMA). In the present study, the effect of MDMA on brain energy regulation was 
      investigated by examining the effect of MDMA on brain glycogen and glucose. A 
      single injection of MDMA (10-40 mg/kg, s.c.) produced a dose-dependent decrease 
      (40%) in brain glycogen, which persisted for at least 1 h. MDMA (10 and 40 mg/kg, 
      s.c.) also produced a significant and sustained increase in the extracellular 
      concentration of glucose in the striatum. Subjecting rats to a cool ambient 
      temperature of 17 degrees C significantly attenuated MDMA-induced hyperthermia 
      and glycogenolysis. MDMA-induced glycogenolysis also was prevented by treatment 
      of rats with the 5-hydroxytryptamine(2) (5-HT(2)) antagonists 
      6-methyl-1-(1-methylethyl)-ergoline-8 beta-carboxylic acid 2-hydroxy-1 
      methylprophyl ester maleate (LY-53,857; 3 mg/kg i.p.), desipramine (10 mg/kg 
      i.p.), and iprindole (10 mg/kg i.p.). LY-53,857 also attenuated the MDMA-induced 
      increase in the extracellular concentration of glucose as well as MDMA-induced 
      hyperthermia. Amphetamine analogs (e.g., methamphetamine and 
      parachloroamphetamine) that produce hyperthermia also produced glycogenolysis, 
      whereas fenfluramine, which does not produce hyperthermia, did not alter brain 
      glycogen content. These results support the conclusion that MDMA induces 
      glycogenolysis and that the process involves 5-HT(2) receptor activation. These 
      results are supportive of the view that MDMA promotes energy dysregulation and 
      that hyperthermia may play an important role in MDMA-induced alterations in 
      cellular energetics.
FAU - Darvesh, Altaf S
AU  - Darvesh AS
AD  - College of Pharmacy, University of Cincinnati, Cincinnati, Ohio 45267, USA.
FAU - Shankaran, Mahalakshmi
AU  - Shankaran M
FAU - Gudelsky, Gary A
AU  - Gudelsky GA
LA  - eng
GR  - DA07427/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Hallucinogens)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Serotonin Antagonists)
RN  - 9005-79-2 (Glycogen)
RN  - IY9XDZ35W2 (Glucose)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Animals
MH  - Body Temperature/drug effects/physiology
MH  - Brain Chemistry/*drug effects
MH  - Corpus Striatum/drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Space/drug effects/metabolism
MH  - Fever/chemically induced
MH  - Glucose/*metabolism
MH  - Glycogen/*metabolism
MH  - Hallucinogens/*pharmacology
MH  - Male
MH  - Microdialysis
MH  - N-Methyl-3,4-methylenedioxyamphetamine/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Serotonin/drug effects
MH  - Serotonin Antagonists/pharmacology
EDAT- 2002/03/22 10:00
MHDA- 2002/04/19 10:01
CRDT- 2002/03/22 10:00
PHST- 2002/03/22 10:00 [pubmed]
PHST- 2002/04/19 10:01 [medline]
PHST- 2002/03/22 10:00 [entrez]
AID - 10.1124/jpet.301.1.138 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2002 Apr;301(1):138-44. doi: 10.1124/jpet.301.1.138.