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
Method to Extend Research in Time (MERIT) Award (R37)
Project #
3R37DA004788-21S1
Application #
7281064
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Pilotte, Nancy S
Project Start
1990-08-01
Project End
2008-02-29
Budget Start
2006-07-01
Budget End
2007-02-28
Support Year
21
Fiscal Year
2006
Total Cost
$41,035
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; Spencer, Robert C; Harris, Rachel L et al. (2014) The effects of clinically relevant doses of amphetamine and methylphenidate on signal detection and DRL in rats. Neuropharmacology 79:634-41
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
Perry, Michelle L; Andrzejewski, Matthew E; Bushek, Susan M et al. (2010) Intra-accumbens infusion of a muscarinic antagonist reduces food intake without altering the incentive properties of food-associated cues. Behav Neurosci 124:44-54
Perry, Michelle L; Baldo, Brian A; Andrzejewski, Matthew E et al. (2009) Muscarinic receptor antagonism causes a functional alteration in nucleus accumbens mu-opiate-mediated feeding behavior. Behav Brain Res 197:225-9