Heroin and cocaine abuse and addict recidivism are serious problems in our society. The powerful positive reinforcing properties of these agents are generally believed to be primarily responsible for this behavior. It is hoped that a better understanding of the neurobiologic principles and components of brain reinforcement mechanisms in general, and how and where these agents interact with this system in particular, will help address this problem. As such, the specific aims of this proposal are to : define those anatomic sites and circuits activated by heroin and cocaine; to determine the anatomic substrates where these agents become conditioned to neutral stimuli;and finally, to define those sites which are common vs. independent to heroin and cocaine reward vs. natural (food) reward. To accomplish these aims, an autoradiographic, metabolic mapping procedure with computerized densitometric image analysis will be employed. Using a technique to measure functional changes after relatively short (2 min) time points vs. the more classic, 45-min 2-DG procedure, one can essentially take a """"""""snapshot"""""""" of the entire neuronal response to a given stimulus. It is hoped that a better understanding of the functional anatomy of both the unconditional (pharmacologic) and conditional properties of these drugs of abuse will be obtained. Finally, by comparing responses across drug classes (psycho-stimulants and opiates) and between these artificial and natural reinforcers, one should be able to examine those elements of brain common to reinforcers as a class. Those unique elements found might represent individual reward initiation sites independently entering a common reinforcement substrate. The distinction between reinforcers might then depend upon where (i.e., which neuronal elements) the initiation site tapped into this brain reward circuit. The significance of these studies should be to provide a) a better understanding of the brain's drive-reward system and b) a picture of regions amenable to conditioning and how this might be applied to post addict therapies.
