A key to understanding addiction and other compulsive behaviors will be to reveal the means by which environmental cues (conditioned stimuli, CS) associated with primary rewards (palatable food or addictive drugs) come to generate both approach responses to the location where reward is expected and more complex operants associated with reward procurement. In order to understand the dysfunction of these processes, it is critical to understand their neural bases under normal conditions. The nucleus accumbens is anatomically connected as an interface between limbic motivational circuitry and the motor system, and has been strongly implicated in reward processes. However, it remains unclear 1) whether accumbens processing of a reward-paired CS and behavioral responses can be localized to the two anatomically and functionally distinct accumbens subregions, the core and shell;2) whether individual accumbens neurons associated with the CS and behavioral response also encode the strength of the animal's reward expectation. 3) how levels of DA transmission interact with reward expectation strength to determine whether or not an approach response will be generated. Here, single-neuron recordings in the accumbens core or shell will be obtained in parallel with intra-accumbens microinjections of DA antagonists, employing identical behavioral paradigms. Reward expectation will be manipulated by presenting CSs that predict food delivery with varying probability or magnitude. Another set of experiments will ask whether accumbens responses code for the specific behavioral act, the specifc reward expected, and/or the behavior/reward conjunction. It is predicted that 1) neurons in the medial shell will be more responsive to the CS than neurons in the core;while neurons in the core will show greater firing during the behavioral response than neurons in the medial shell;2) these cells will reflect the strength of the animal's reward expectation, 3) D1 receptor blockade will increase the threshold for CSs signaling varying levels of reward expectation to trigger approach responses, and 4) populations of accumbens neurons will be found to encode specific response-reward relationships. Regardless of the direction of results, the findings will contribute to a clearer neurobiological understanding of accumbens shell and core involvement in reward processes, without which the current state of knowledge may not lead to the development of effective strategies for treating addictions.Relevance The proposed experiments will shed light upon the neurobiological mechanisms underlying addiction and compulsive behaviors. Past research strongly suggests that the nucleus accumbens is a key site in the brain circuits by which natural rewards (such as food) as well as drug rewards (such as cocaine) acquire the ability to powerfully control human behavior. These studies, which examine the responses of neurons in this brain area to environmental stimuli associated with natural reward, will provide key insights regarding the manner in which reward-associated environmental stimuli produce normal and abnormal reward-driven behaviors.
