Tags

Type your tag names separated by a space and hit enter

Effect of glucoprivation on serotonin neurotoxicity induced by substituted amphetamines.
J Pharmacol Exp Ther 2002; 303(2):831-9JP

Abstract

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.

Authors+Show Affiliations

Department of Neurology, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12388670

Citation

Yuan, Jie, et al. "Effect of Glucoprivation On Serotonin Neurotoxicity Induced By Substituted Amphetamines." The Journal of Pharmacology and Experimental Therapeutics, vol. 303, no. 2, 2002, pp. 831-9.
Yuan J, Cord BJ, McCann UD, et al. Effect of glucoprivation on serotonin neurotoxicity induced by substituted amphetamines. J Pharmacol Exp Ther. 2002;303(2):831-9.
Yuan, J., Cord, B. J., McCann, U. D., Callahan, B. T., & Ricaurte, G. A. (2002). Effect of glucoprivation on serotonin neurotoxicity induced by substituted amphetamines. The Journal of Pharmacology and Experimental Therapeutics, 303(2), pp. 831-9.
Yuan J, et al. Effect of Glucoprivation On Serotonin Neurotoxicity Induced By Substituted Amphetamines. J Pharmacol Exp Ther. 2002;303(2):831-9. PubMed PMID: 12388670.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of glucoprivation on serotonin neurotoxicity induced by substituted amphetamines. AU - Yuan,Jie, AU - Cord,Branden J, AU - McCann,Una D, AU - Callahan,Brian T, AU - Ricaurte,George A, PY - 2002/10/22/pubmed PY - 2002/11/26/medline PY - 2002/10/22/entrez SP - 831 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 303 IS - 2 N2 - 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/12388670/Effect_of_glucoprivation_on_serotonin_neurotoxicity_induced_by_substituted_amphetamines_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=12388670 DB - PRIME DP - Unbound Medicine ER -