Year: 2012
Type: article
Abstract: ±-3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a ring-substituted amphetamine derivative, and a popular psychoactive drug of abuse.This drug evokes a well-documented acute increase in the release of serotonin, dopamine, and acetylcholine, as well as persistent reductions in markers of serotonin axon terminals across several brain regions.Little is known concerning the effect of MDMA exposure on the glutamatergic neurotransmitter system.Excitotoxicity resulting from excessive glutamate release has the potential to contribute to the long-term toxicity of MDMA, including neurochemical and behavioral deficits.The purpose of the present study was to assess the effect of repeated MDMA exposure on extracellular glutamate concentrations in the rat brain, the mechanism(s) underlying this potential response, and the potential behavioral consequences of altered glutamate release.It was found that two and four injections of MDMA (10 mg/kg, i.p.), but not one, significantly elevated the concentration of extracellular glutamate in the dorsal hippocampus.Furthermore, this increase was not observed in either the prefrontal cortex or the striatum.Direct infusion of MDMA to the hippocampus evoked a similar increase, suggesting a local, intrahippocampal site of action of the drug.Furthermore, serotonergic signaling through the 5HT2A/C receptor was implicated in the underlying mechanism of glutamate release by the attenuation of the MDMA effect with either the SSRI fluoxetine or the 5-HT2A/C inhibitor ketanserin.Local administration of the sodium-channel blocker TTX did not prevent the MDMA-induced increase in glutamate efflux, indicating a non-neuronal, e.g.glial, source of glutamate release.In agreement with this conclusion is the finding that pharmacological modulation of glutamate regulatory mechanisms, including me with so much support along the way, both material and moral, that I could not have completed my project or become who I am today without them.Additionally, I would like to say a special thanks to my advisor, Dr. Gary Gudelsky.I greatly appreciate being able to study and work in his lab, as well as the guidance and
Author: John H. Anneken
Institution: University of Cincinnati
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W2253094669