2‐Deoxy‐D‐Glucose Prevents and Nicotinamide Potentiates 3,4‐Methylenedioxymethamphetamine‐Induced Serotonin Neurotoxicity
Isabel Hervias, Berta Lasheras, Norberto Aguirre
Journal of Neurochemistry September 1, 2000 DOI: 10.1046/j.1471-4159.2000.0750982.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA Nicotinamide |
| Dose | MDMA 15 mg/kg i.p. |
| Duration | Up to 3 hours for ATP measurements; long-term for serotonin deficits |
| Topics | MDMA Serotonin |
| Key findings | 2-DG prevented MDMA-induced serotonin deficits in the frontal cortex, hippocampus, and striatum, but this protection was abolished when hypothermia was prevented. Nicotinamide potentiated MDMA-induced serotonin deficits. MDMA did not change ATP concentrations up to 3 hours after administration, suggesting altered energy metabolism is not the main cause of MDMA neurotoxicity. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Studies on the mechanisms underlying amiloride enhancement of 3,4-methylenedioxymethamphetamine-induced serotonin depletion in rats. European Journal of Pharmacology May 21, 2007
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- Molecular and Cellular Mechanisms of Ecstasy-Induced Neurotoxicity: An Overview Molecular Neurobiology June 1, 2009
- Phosphodiesterase 5 inhibitors prevent 3,4-methylenedioxymethamphetamine-induced 5-HT deficits in the rat. Journal of Neurochemistry February 2009
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