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 Since preliminary results have shown increased GluR1 surface expression in rats withdrawn from repeated cocaine exposure, Aim 2 will investigate other possible changes in the surface expression of AMPA, NMDA, and DA receptors in the NAc in this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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
5F30DA019762-04
Application #
7388821
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2005-04-04
Project End
2008-10-03
Budget Start
2008-04-04
Budget End
2008-10-03
Support Year
4
Fiscal Year
2008
Total Cost
$17,438
Indirect Cost
Name
Rosalind Franklin University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
069501252
City
North Chicago
State
IL
Country
United States
Zip Code
60064