PMID- 12388670
OWN - NLM
STAT- MEDLINE
DCOM- 20021122
LR  - 20221207
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 303
IP  - 2
DP  - 2002 Nov
TI  - Effect of glucoprivation on serotonin neurotoxicity induced by substituted 
      amphetamines.
PG  - 831-9
AB  - The present studies were conducted to further explore the potential role of 
      metabolic compromise in substituted amphetamine-induced serotonin (5-HT) 
      neurotoxicity. To this end, we examined the glucoprivic effects of 
      2-deoxy-D-glucose (2-DG) on the 5-HT neurotoxic effects of fenfluramine (FEN) and 
      methylenedioxymethamphetamine (MDMA). Rats were treated with either FEN or MDMA, 
      alone and in combination, with doses of 2-DG known to produce glucoprivic effects 
      at either 22 +/- 1 or 28 +/- 1 degrees C. At 22 +/- 1 degrees C, FEN produced 
      hypothermia, MDMA induced hyperthermia, and both drugs produced significant 
      long-term reductions in regional brain 5-HT neuronal markers. 2-DG did not 
      enhance 5-HT neurotoxicity induced by either FEN or MDMA; indeed, in some 
      instances, it afforded partial neuroprotection. Although 2-DG afforded partial 
      protection from both FEN and MDMA-induced 5-HT neurotoxic changes, it also caused 
      significant hypothermia, raising the possibility that protection was due to a 
      lowered temperature. Increasing the ambient temperature to 28 +/- 1 degrees C 
      largely eliminated drug-induced hypothermia and eliminated the neuroprotective 
      effects of 2-DG. Thus, even without the confounding effect of temperature, 2-DG 
      still did not potentiate FEN or MDMA-induced 5-HT neurotoxicity. These findings 
      suggest that the role of metabolic compromise in amphetamine-induced 5-HT 
      neurotoxicity merits further study.
FAU - Yuan, Jie
AU  - Yuan J
AD  - Department of Neurology, Johns Hopkins University School of Medicine, 5501 
      Hopkins Bayview Circle, Baltimore, MD 21224, USA.
FAU - Cord, Branden J
AU  - Cord BJ
FAU - McCann, Una D
AU  - McCann UD
FAU - Callahan, Brian T
AU  - Callahan BT
FAU - Ricaurte, George A
AU  - Ricaurte GA
LA  - eng
GR  - DA 05707/DA/NIDA NIH HHS/United States
GR  - DA 05938/DA/NIDA NIH HHS/United States
GR  - DA 10217/DA/NIDA NIH HHS/United States
GR  - DA09487/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 (Amphetamines)
RN  - 0 (Antimetabolites)
RN  - 0 (Biogenic Monoamines)
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Serotonin Agents)
RN  - 0 (Serotonin Plasma Membrane Transport Proteins)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - 0 (Slc6a4 protein, rat)
RN  - 2DS058H2CF (Fenfluramine)
RN  - 333DO1RDJY (Serotonin)
RN  - 54-16-0 (Hydroxyindoleacetic Acid)
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - IY9XDZ35W2 (Glucose)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
SB  - IM
MH  - Amphetamines/*toxicity
MH  - Animals
MH  - Antimetabolites/pharmacology
MH  - Biogenic Monoamines/metabolism
MH  - Body Temperature/physiology
MH  - Carrier Proteins/metabolism
MH  - Deoxyglucose/pharmacology
MH  - Energy Metabolism/drug effects
MH  - Fenfluramine/pharmacology
MH  - Glucose/*physiology
MH  - Hydroxyindoleacetic Acid/metabolism
MH  - Male
MH  - Membrane Glycoproteins/metabolism
MH  - *Membrane Transport Proteins
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Nerve Degeneration/chemically induced/prevention & control
MH  - *Nerve Tissue Proteins
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Serotonin/metabolism/*toxicity
MH  - Serotonin Agents/pharmacology
MH  - Serotonin Plasma Membrane Transport Proteins
MH  - Selective Serotonin Reuptake Inhibitors/pharmacology
EDAT- 2002/10/22 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/10/22 04:00
PHST- 2002/10/22 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/10/22 04:00 [entrez]
AID - 10.1124/jpet.102.041277 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2002 Nov;303(2):831-9. doi: 10.1124/jpet.102.041277.