Matthew E. Andrzejewski - US grants

DESCRIPTION (provided by applicant): Drug addiction and learning are intertwined on at least two levels. The effects of behavioral contingencies (e.g., Pavlovian) on withdrawal, cravings, and motivations for drugs extended the field of learning into that of drug abuse. Contemporary theories that treat drugs as reinforcers, thereby classifying drug abuse as behavior reinforced by its consequences, or in other words, operant behavior, has also bridged drug abuse and learning theory. Thus, the conceptualization of drug-taking, -seeking, abuse, and addiction in the terms of learning theory has been one of the most significant advances in the fields of drug abuse and experimental psychology. Concurrent with the developments in learning theory, neuroscientists were discovering that the neurophysiological changes that accompany learning appear to be mediated by the mesocorticolimbic pathway, a pathway known for its modulation of the effects of drugs as well. Our understanding of this system's basic evolutionary function, however, is still not well-known. Thus, I propose to explore part of the network that instantiates operant learning, especially circuitry in the nucleus accumbens and amygdaloid complex through NMDA and D 1 receptor activation. The proposed research integrates cannula mapping techniques, pharmacological manipulations and advanced behavioral analysis.

DESCRIPTION (provided by applicant): 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.