This application proposes to assess the acute and chronic effects of methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) on dopamine (DA) and serotonin (5-HT) terminal function and evaluate the relationship between DA and 5-HT neurotoxicity. We will first compare the effects of METH and MDMA on monoamine terminal function acutely in mouse brain slices. Then we will evaluate terminal function recovery following a repeated administration paradigm. Voltammetry at carbon fiber electrodes will be used to measure release and uptake of DA and 5-HT in brain slices. With the use of the DA and the 5-HT transporter knockout mouse lines, and the selective neurotoxins phentermine and fenfluramine, we will evaluate whether DA influences 5-HT neurotoxicity, and vice versa. The research proposed will provide valuable insights into the differential long-term impact of amphetamine derivatives on monoamine systems and the potential interactions between DA and 5-HT in inducing neurotoxicity.
| John, Carrie E; Jones, Sara R (2007) Voltammetric characterization of the effect of monoamine uptake inhibitors and releasers on dopamine and serotonin uptake in mouse caudate-putamen and substantia nigra slices. Neuropharmacology 52:1596-605 |
| John, Carrie E; Budygin, Evgeny A; Mateo, Yolanda et al. (2006) Neurochemical characterization of the release and uptake of dopamine in ventral tegmental area and serotonin in substantia nigra of the mouse. J Neurochem 96:267-82 |
| Mathews, Tiffany A; John, Carrie E; Lapa, Gennady B et al. (2006) No role of the dopamine transporter in acute ethanol effects on striatal dopamine dynamics. Synapse 60:288-94 |
| John, Carrie E; Jones, Sara R (2006) Exocytotic release of dopamine in ventral tegmental area slices from C57BL/6 and dopamine transporter knockout mice. Neurochem Int 49:737-45 |
