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Ketamine Pretreatment Exacerbated 3,4-Methylenedioxymethamphetamine-Induced Central Dopamine Toxicity

並列摘要


Currently, joint use of ketamine and 3, 4-methylenedioxymethamphetamine (MDMA, Ecstasy) represents a specific combination of polydrug abuse. Long-lasting and even aggravated central neuronal toxicity associated with mixing ketamine and MDMA use is of especially concern. This study was undertaken to examine the modulating effects of ketamine treatment on later MDMA-induced dopamine and serotonin neurotoxicity. We found that repeated administration of ketamine (50mg/kg×7) at 1.5-h intervals did not render observable dopamine or serotonin depletion in catecholaminergic target regions examined. In contrast, three consecutive doses of MDMA (20mg/kg each) at 2-h intervals produced long-lasting dopamine and serotonin depletions in striatum, nucleus accumbens and prefrontal cortex. More importantly, pretreatment with binge doses of ketamine (50mg/kg×7 at 1.5-h intervals) 12 h prior to the MDMA dosing regimen (20mg/kg×3 at 2-h intervals) aggravated the MDMA-induced dopaminergic toxicity. Nonetheless, such binge doses of ketamine treatment did not affect MDMA induced serotonergic toxicity. These results, taken together, indicate that binge use of ketamine specifically enhances the MDMA-induced central dopaminergic neurotoxicity in adult mouse brain.

並列關鍵字

ecstasy serotonin dopamine anesthetic DAT VMAT-2

參考文獻


Armstrong, B.D.,Noguchi, K.K.(2004).The neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine on serotonin, dopamine, and GABA-ergic terminals: an in-vitro autoradiographic study in rats.Neurotoxicology.25,905-914.
Callahan, B.T.,Cord, B.J.,Yuan, J.,McCann, U.D.,Ricaurte, G.A.(2001).Inhibitors of Na(+)/H(+) and Na(+)/Ca(2+) exchange potentiate methamphetamine-induced dopamine neurotoxicity: possible role of ionic dysregulation in methamphetamine neurotoxicity.J. Neurochem..77,1348-1362.
Darvesh, A.S.,Gudelsky, G.A.(2005).Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT.Brain Res..1056,168-175.
Farfel, G.M.,Seiden L.S.(1995).Role of hypothermia in the mechanism of protection against serotonergic toxicity. I. Experiments using 3,4-methylenedioxymethamphetamine, dizocilpine, CGS 19755 and NBQX.J. Pharm. Exper. Ther..272,860-867.
Finnegan, K.T.,Taraska, T.(1996).Effects of glutamate antagonists on methamphetamine and 3,4-methylenedioxymethamphetamine-induced striatal dopamine release in vivo.J. Neurochem..66,1949-1958.

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