Conditioned reinforcement is the process whereby cues that have been paired with primary rewards support the acquisition and maintenance of new instrumental responses. Abnormal responding to such cues is a prominent feature of drug addiction, where drug-associated cues motivate drug-taking and relapse in addicts and in laboratory animals in animal models of drug seeking and relapse. The efficacy of drug-associated cues in animal models depends on circuits that take information from the basolateral amygdala (ABL) to orbitofrontal cortex (OFC) or nucleus accumbens (NAc);however, interpreting these data is hampered by our limited understanding of how these circuits (e.g., ABL-OFC or ABL-NAc) normally support conditioned reinforcement. Here we hypothesize that these circuits support conditioned reinforcement due to their differing roles in Pavlovian associative learning. Output from ABL to OFC is critical to allowing cues to become associated with the value of the outcome (e.g., drug or food availability) Pavlovian cues predict, whereas output from ABL to NAc appears to be critical for the formation of associations between cues and the general affect or emotion (e.g., happiness, fear) evoked by the outcome. Since addictive drugs have divergent effects on these two circuits, they may cause an imbalance in what associative information (outcome-specific mediated by ABL- OFC versus general affect mediated by ABL-NAc) is recruited by drug-associated cues to guide behavior. Here, we will test the hypotheses outlined above. We will train rats to associate cues with the appetitive reward (sucrose) using Pavlovian training procedures that emphasize one or the other type of representation (outcome-specific or general affect). We will then test whether these specialized cues support conditioned reinforcement in normal rats and in rats with lesions of the ABL-OFC or the ABL-NAc circuits. In addition, we will identify neural correlates of conditioned reinforcement for these specialized cues in each circuit. Finally, we will test the effects of cocaine self-administration on conditioned reinforcement for different types of cues and neural correlates of conditioned reinforcement. The results will provide a neuroanatomical framework with which to better understand how reward-associated cues exert effects on behavior under normal (drug-na?ve) conditions and after exposure to cocaine.
Conditioned reinforcement is the process whereby cues that have been paired with primary rewards support the acquisition and maintenance of new instrumental responses. Abnormal responding to such cues is a prominent feature of drug addiction, where drug-associated cues motivate drug-taking and relapse in addicts and animal models. The efficacy of drug-associated cues in animal models depends on circuits that take information from the basolateral amygdala (ABL) to orbitofrontal cortex (OFC) or nucleus accumbens (NAc); however interpreting these data is hampered by our limited understanding of how these circuits (e.g. ABL-OFC or ABL-NAc) normally support conditioned reinforcement. Here, we will identify the different neural circuits mediating conditioned reinforcement and further localize the effects of chronic cocaine use on encoding of conditioned reinforcers in these circuits. The results will provide a neuroanatomical framework with which to better understand how reward-associated cues exert effects on behavior under normal (drug-na?ve) conditions and after exposure to cocaine.
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