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2-Deoxy-D-glucose prevents and nicotinamide potentiates 3, 4-methylenedioxymethamphetamine-induced serotonin neurotoxicity.
J Neurochem 2000; 75(3):982-90JN

Abstract

Neurotoxicity induced by different substituted amphetamines has been associated with the exhaustion of intracellular energy stores. Accordingly, we examined the influence of 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glucose uptake and metabolism, and nicotinamide, an agent that improves energy metabolism, on 3, 4-methylenedioxymethamphetamine (MDMA)-induced 5-hydroxytryptamine (5-HT; serotonin) deficits. Administration of MDMA (15 mg/kg i.p.) produced a significant hyperthermia, whereas 2-DG caused a profound hypothermia that lasted throughout the experiment. When MDMA was given to 2-DG-treated rats, an immediate but transient hyperthermia occurred and was followed by a return to hypothermia. 2-DG had no effect on 5-HT concentrations in the frontal cortex, hippocampus, and striatum but prevented the neurotoxicity induced by MDMA. When rats were injected with 2-DG/MDMA and were warmed to prevent hypothermia, the protection afforded by 2-DG was abolished. Nicotinamide had no effect on body temperature of the rats, and the hyperthermia induced by the nicotinamide/MDMA treatment was similar to that of the saline/MDMA-treated rats. However, the long-term 5-HT deficits induced by MDMA were potentiated by nicotinamide in all the brain regions examined. Finally, no change on ATP concentrations in the frontal cortex, hippocampus, and striatum was observed up to 3 h after a single dose of MDMA. These results suggest that an altered energy metabolism is not the main cause of the neurotoxic effects induced by MDMA.

Authors+Show Affiliations

Department of Pharmacology, University of Navarra Medical School, Pamplona, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10936179

Citation

Hervías, I, et al. "2-Deoxy-D-glucose Prevents and Nicotinamide Potentiates 3, 4-methylenedioxymethamphetamine-induced Serotonin Neurotoxicity." Journal of Neurochemistry, vol. 75, no. 3, 2000, pp. 982-90.
Hervías I, Lasheras B, Aguirre N. 2-Deoxy-D-glucose prevents and nicotinamide potentiates 3, 4-methylenedioxymethamphetamine-induced serotonin neurotoxicity. J Neurochem. 2000;75(3):982-90.
Hervías, I., Lasheras, B., & Aguirre, N. (2000). 2-Deoxy-D-glucose prevents and nicotinamide potentiates 3, 4-methylenedioxymethamphetamine-induced serotonin neurotoxicity. Journal of Neurochemistry, 75(3), pp. 982-90.
Hervías I, Lasheras B, Aguirre N. 2-Deoxy-D-glucose Prevents and Nicotinamide Potentiates 3, 4-methylenedioxymethamphetamine-induced Serotonin Neurotoxicity. J Neurochem. 2000;75(3):982-90. PubMed PMID: 10936179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 2-Deoxy-D-glucose prevents and nicotinamide potentiates 3, 4-methylenedioxymethamphetamine-induced serotonin neurotoxicity. AU - Hervías,I, AU - Lasheras,B, AU - Aguirre,N, PY - 2000/8/11/pubmed PY - 2000/9/19/medline PY - 2000/8/11/entrez SP - 982 EP - 90 JF - Journal of neurochemistry JO - J. Neurochem. VL - 75 IS - 3 N2 - Neurotoxicity induced by different substituted amphetamines has been associated with the exhaustion of intracellular energy stores. Accordingly, we examined the influence of 2-deoxy-D-glucose (2-DG), a competitive inhibitor of glucose uptake and metabolism, and nicotinamide, an agent that improves energy metabolism, on 3, 4-methylenedioxymethamphetamine (MDMA)-induced 5-hydroxytryptamine (5-HT; serotonin) deficits. Administration of MDMA (15 mg/kg i.p.) produced a significant hyperthermia, whereas 2-DG caused a profound hypothermia that lasted throughout the experiment. When MDMA was given to 2-DG-treated rats, an immediate but transient hyperthermia occurred and was followed by a return to hypothermia. 2-DG had no effect on 5-HT concentrations in the frontal cortex, hippocampus, and striatum but prevented the neurotoxicity induced by MDMA. When rats were injected with 2-DG/MDMA and were warmed to prevent hypothermia, the protection afforded by 2-DG was abolished. Nicotinamide had no effect on body temperature of the rats, and the hyperthermia induced by the nicotinamide/MDMA treatment was similar to that of the saline/MDMA-treated rats. However, the long-term 5-HT deficits induced by MDMA were potentiated by nicotinamide in all the brain regions examined. Finally, no change on ATP concentrations in the frontal cortex, hippocampus, and striatum was observed up to 3 h after a single dose of MDMA. These results suggest that an altered energy metabolism is not the main cause of the neurotoxic effects induced by MDMA. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/10936179/2_Deoxy_D_glucose_prevents_and_nicotinamide_potentiates_3_4_methylenedioxymethamphetamine_induced_serotonin_neurotoxicity_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0022-3042&date=2000&volume=75&issue=3&spage=982 DB - PRIME DP - Unbound Medicine ER -