Although the past fifteen years of research has provided a wealth of insight into the neurobiological basis of drug addiction, society as a whole remains heavily impacted by drugs of abuse. More research is needed to further understand the cellular basis of the persistent behaviors associated with drug addiction (seeking, craving, and relapse to use) to help provide better treatment strategies to combat addiction. Our hypothesis is that addiction is a form of neuronal plasticity, perhaps an aberrant form of learning, similar in mechanism to other forms of plasticity, such as LTD and LTP. This research proposal will provide important information about the biochemical plasticity of the nucleus accumbens (NAc), a brain region important for the motivational aspects of behavior and essential in drug addiction. This will further our understanding of addictionrelated adaptations on the cellular level. Because LTP in some brain regions is mediated by AMPA and NMDA receptor trafficking and a direct link between the altered glutamate systems in animals exposed to psychostimulants and dopamine receptor stimulation has recently emerged, I propose to investigate the biochemical mechanisms of ionotropic glutamate trafficking and the role that DA receptors may have in the NAc.
Aim 1 will investigate the underlying biochemistry of AMPA receptor trafficking and its acute regulation by DA receptors in acute, naive NAc tissue slices. Since preliminary results have shown increased GluR1 surface expression in rats withdrawn from repeated cocaine exposure, Aim 2 will investigate other possible changes in the surface expression of AMPA, NMDA, and DA receptors in the NAc in this animal model. Our results may describe a mechanistic link between the biochemistry of NAc glutamate receptor trafficking and the neuroplasticty that occurs in drug addiction.
| Boudreau, Amy C; Milovanovic, Mike; Conrad, Kelly L et al. (2012) A protein cross-linking assay for measuring cell surface expression of glutamate receptor subunits in the rodent brain after in vivo treatments. Curr Protoc Neurosci Chapter 5:Unit 5.30.1-19 |
| Boudreau, Amy C; Ferrario, Carrie R; Glucksman, Marc J et al. (2009) Signaling pathway adaptations and novel protein kinase A substrates related to behavioral sensitization to cocaine. J Neurochem 110:363-77 |
| Boudreau, Amy C; Reimers, Jeremy M; Milovanovic, Michael et al. (2007) Cell surface AMPA receptors in the rat nucleus accumbens increase during cocaine withdrawal but internalize after cocaine challenge in association with altered activation of mitogen-activated protein kinases. J Neurosci 27:10621-35 |
| Boudreau, Amy C; Wolf, Marina E (2005) Behavioral sensitization to cocaine is associated with increased AMPA receptor surface expression in the nucleus accumbens. J Neurosci 25:9144-51 |
