Associate Provost for Research Boston University Medical Campus
NIDA - National Institute on Drug Abuse	Research Resources

Abstract

Abstract: DESCRIPTION (provided by applicant): 3,4-methylenedioxymethamphetamine is a widely abused recreational amphetamine derivative that is known to cause damage to serotonin (5-HT) neurons in animals and possibly humans. The goal of this proposal is to determine the role of 5-HT1B and 5-HT2C in mediating the unique neurochemical effects of this drug that may underlie its unique psychological, behavioral and toxic effects. Previous work has suggested a role for these 5-HT receptors in mediating the effects of MDMA, but has stopped short of defining the role of 5-HT interactions with other neurotransmitters such as GABA or dopamine. By using the technique of in vivo microdialysis and HPLC, I will define the effects of MDMA induced release of 5-HT acting at 5-HT1B and 5-HT2C receptors on GABA release in the ventral tegmental area (VTA) and subsequent modulation of DA release in the nucleus accumbens, an area of the brain associated with motivational and addictive behaviors. In addition to characterizing the acute effects of MDMA in these important brain regions, evaluation of the interactions of 5-HT with GABA and dopamine will be assessed in animals that have received a neurotoxic regimen of MDMA. This will determine the neurochemical consequences of MDMA-induced neurotoxicity and provide insight into the mechanisms that underlie the long-term negative psychological effects associated with MDMA.

Thesaurus Terms:
3,4 methylenedioxymethamphetamine, dopamine, drug interaction, gamma aminobutyrate, serotonin
biological signal transduction, dosage, drug abuse, neurochemistry, neuropharmacology, neurotoxicology, neurotransmitter, nucleus accumbens, serotonin receptor, tegmentum
high performance liquid chromatography, laboratory rat, microdialysis, postdoctoral investigator

Institution:	BOSTON UNIVERSITY MEDICAL CAMPUS
	715 ALBANY ST, 560
	BOSTON, MA 021182394
Fiscal Year:	2005
Department:	PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Project Start:	13-JUN-2003
Project End:	12-JUN-2006
ICD:	NATIONAL INSTITUTE ON DRUG ABUSE
IRG:	NIDA