The clinical course of cocaine abuse has been characterized as progressing through a number of temporal stages that advance from initial experimentation to addiction. This clinical course is paralleled by changes in the neurobiological response to cocaine, as well as residual changes in function and structure that can persist despite periods of abstinence. During the past finding period we have employed a non-human primate model of cocaine self-administration to map the constellation of cerebral metabolic changes associated with the initial phases of self-administration and compared these effects to those that occur following chronic exposure (3.3 months). In addition, we have characterized the topography of changes in markers of the dopamine system that result from continued cocaine self administration. Increasing durations of cocaine exposure produced an intensification and widening of metabolic and structural changes across functional domains in the non-human primate brain. This change in functional topography suggests a marked change in the response to cocaine as a consequence of duration drug history. Given this, two questions arise. First, is there a continued progression of change in structure and function with increasing durations of self-administration history? Second, is there a reversal of topographic alterations following cessation of drug taking? In the present proposal the functional effects of 1.5 years of cocaine self-administration will be assessed. In addition, the effects of abstinence (1 and 3 months) following moderate and prolonged periods of self-administration on these functional markers will be measured. Identifying these changes will provide the basis for clearer evaluations of treatment strategies whether pharmacological or behavioral.
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