? 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. ? ? ? ?
|Amato, Jennifer L; Bankson, Michael G; Yamamoto, Bryan K (2007) Prior exposure to chronic stress and MDMA potentiates mesoaccumbens dopamine release mediated by the 5-HT(1B) receptor. Neuropsychopharmacology 32:946-54|
|Yamamoto, Bryan K; Bankson, Michael G (2005) Amphetamine neurotoxicity: cause and consequence of oxidative stress. Crit Rev Neurobiol 17:87-117|
|Bankson, Michael G; Yamamoto, Bryan K (2004) Serotonin-GABA interactions modulate MDMA-induced mesolimbic dopamine release. J Neurochem 91:852-9|