In recent years a great amount of interest has focused on the role of dopamine-glutamate interactions in the control of neural plasticity, learning and memory, and addiction. These two neurotransmitter systems are found widely distributed in many regions of cortex, limbic system, and basal ganglia, where they appear to play an integrative role in motivational and associative information processing. It is currently believed that coordinated neural signaling of these systems, particularly through the dopamine D1 and glutamate N-methyI-D-aspartate (NMDA) receptors, is a critical event in triggering intracellular transductional and transcriptional cascades that lead to long-term changes in gene expression, synaptic plasticity, and ultimately behavior. Addictive drugs also induce long-term neuroadaptations at the structural, cellular, molecular, and genomic levels, primarily through their impact on dopaminergic and glutamatergic circuits. Such drug-induced neuroadaptations may contribute to abnormal information processing and behavior, resulting in poor decision-making, loss of control, and compulsivity that characterized addiction. Thus, further information regarding the normal behavioral role of dopamine- and glutamate-mediate neural networks may help to shed light on the nature of addiction and its treatment. In this research project, the role of glutamate- and dopamine-coded neural circuitry in the control of appetitive instrumental learning will be explored. Using anatomical, molecular, and behavioral approaches, we will test the hypothesis that NMDA- and Dl-receptor mediated plasticity within multiple nodes of a neural network controls new adaptive motor learning.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA004788-22
Application #
7189909
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Pilotte, Nancy S
Project Start
1990-08-01
Project End
2010-02-28
Budget Start
2007-03-01
Budget End
2010-02-28
Support Year
22
Fiscal Year
2007
Total Cost
$337,164
Indirect Cost
Name
University of Wisconsin Madison
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Andrzejewski, Matthew E; McKee, Brenda L; Baldwin, Anne E et al. (2013) The clinical relevance of neuroplasticity in corticostriatal networks during operant learning. Neurosci Biobehav Rev 37:2071-80
Andrzejewski, Matthew E; Schochet, Terri L; Feit, Elizabeth C et al. (2011) A comparison of adult and adolescent rat behavior in operant learning, extinction, and behavioral inhibition paradigms. Behav Neurosci 125:93-105