DESCRIPTION (provided by applicant): Imaging with PET and [11C] raclopride before and after a pharmacologic challenge provides a reliable and non-invasive measure of changes in endogenous dopamine in the human brain. Previous studies have shown that cocaine dependence is associated with a decrease in dopamine release in response to a psychostimulant challenge. We have recently completed a study demonstrating that this loss of pre-synaptic dopamine function is associated with the choice to self-administer cocaine in the presence of an alternative reinforcer. Importantly, this finding consistent with animal models of reinforcement and which show that dopamine transmission serves to modulate reward based behavior, and in this case, allow for a more adaptive response to be made in the presence of a competing reinforcer.
The previous study was performed in non-treatment seeking cocaine dependent subjects using an inpatient laboratory model to measure the choice for cocaine. Thus, the goal of the present proposal is to investigate this association in a more realistic setting where cocaine dependent out patients face the choice between using cocaine and the alternative reinforcers presented to them in a therapeutic setting. The Community Reinforcement Approach with voucher incentives is a treatment for cocaine dependence that has been shown success in a number of controlled studies. Since the basis of this therapy is to reduce the reinforcing value of cocaine by increasing the density of alternative, healthy reinforcers, we have chosen to correlate outcome from this treatment with measures of presynaptic dopamine function. We propose to scan 40 cocaine dependent patients with [11C] raclopride and oral methylphenidate in order to measure dopamine release. Patients will be scanned before treatment and at 12 weeks into therapy. We predict that the patients with the greatest loss of dopamine transmission at the pre-treatment scan will be those who fail to respond to treatment. Furthermore, we hypothesize that the patients who do respond to treatment will experience a recovery of dopamine function, measured at the post-treatment scan.
To date, no imaging studies of neurochemistry have been performed to investigate the relationship between neurochemistry and response to a behavioral treatment for cocaine dependence. Furthermore, despite the efficacy of this treatment, a substantial proportion of patients are likely to fail to respond. Thus the objectives of this study are to provide a better understanding of the neurobiology associated with treatment failure, with an ultimate goal of developing methods to improve the success of this behavioral therapy.