Background
A major goal of treatments for cocaine addiction is to reduce relapse-associated cravings, which are typically induced by environmental stimuli associated with cocaine use and related to changes in dopamine neurotransmission.
Methods
The present study utilized an animal model of cocaine seeking to determine functional consequences of cue exposure using [18F]fluoro-deoxyglucose (FDG) and PET and to relate findings to juvenile levels of dopamine transporter and D2-like receptor availabilities determined prior to any drug exposure. Adult male rhesus monkeys (N=11) self-administered cocaine (0.2 mg/kg/injection) under a second-order schedule of reinforcement, in which responding was maintained by conditioned reinforcers. PET scans assessing glucose utilization, a marker of functional activation, were conducted during cocaine-cue responding and food-reinforced responding in a context where cocaine was never available.
Results
Compared to the non-cocaine condition, we found significant functional activation in the medial prefrontal cortex, anterior cingulate, precuneus region of the parietal cortex, and striatum; findings similar to those reported in human cocaine abusers. Furthermore, these functional activations in the prefrontal, cingulate and parietal cortex measured during cocaine-cue responding were significantly correlated with juvenile measures of DAT availability, while no significant relationship with prior D2-like receptor availability was observed in any brain region.
Conclusions
The similarity between the present findings and those in human cocaine users supports the use of this model for examination of factors that impact the development and intensity of cue-induced drug seeking, and provide evidence for potential biomarkers for the evaluation of potential treatments (behavioral and pharmacological) for cocaine abuse.