Over the past decade there has been an explosion of knowledge in our understanding of the neurobiological basis of drug addiction, yet this country continues to be plagued by drug related crimes and problems. More research is needed to further characterize the cellular adaptations that take place in response to chronic drug exposure in order to develop pharmacological or better yet behavioral strategies to combat drug addiction. Our hypothesis is that drug addiction is a form of maladaptive synaptic plasticity that uses cellular mechanisms similar to other forms of plasticity like LTP. This research proposal will provide essential information about medium spiny neurons in the nucleus accumbens (NAc), a brain region that converts motivation into behavior and is critically involved in drug abuse, and thereby further our understanding of this maladaptive change at a molecular level. Because previous studies have shown that alterations in glutamate receptor function in NAc are important adaptations triggered by chronic cocaine or amphetamine exposure, we propose to investigate the regulation of glutamate receptor phosphorylation and trafficking regulation of the AMPA receptor subunit GluR1 in LTP and LTD.
Aim 1 will characterize expression of D1 and D2 DA receptors and GluR1 in the cultures. Our preliminary results have shown expression of all three receptors, a mature pattern of GluR1 surface expression and evidence of GluR1 down-regulation in response to high glutamate levels.
Aim 2 will examine the regulation of GluR1 phosphorylation by DA receptor stimulation. In preliminary studies, D1 receptor stimulation increased GluR1 phosphorylation.
Aim 3 will study how DA receptor stimulation affects GluR1 trafficking. Our results may suggest mechanistic links between neuroplasticity in drug addiction and learning.

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 #
1F30DA006024-01
Application #
6136283
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
2000-03-10
Project End
Budget Start
2000-03-10
Budget End
2001-03-09
Support Year
1
Fiscal Year
2000
Total Cost
$31,279
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