Background: Cocaine can elicit drug-seeking behavior for drug-predicting stimuli, even after a single stimulus-cocaine pairing. While orbitofrontal cortex is thought to be important during encoding and maintenance of stimulus-reward value, we still lack a comprehensive model of the neural circuitry underlying this cognitive process.
Methods: We studied the conditioned effects of cocaine using monkey fMRI and classical conditioning by pairing a visual shape (conditioning stimulus, CS+) with a non-contingent cocaine infusion, while a control stimulus (CoS) was never paired. We correlated the monkey’s behavioral preference for the CS+, as measured offline, with the activity induced by the CS+ relative to the CoS as function of time.
Results: We observed that during formation of stimulus-cocaine associations strong CS+-induced fMRI activations emerged in frontal cortex which correlated significantly with behavioral CS+ preference. Afterwards, CS+ preference correlated only with activity in early visual cortex. Control experiments suggest that these findings cannot be explained by increased familiarity for the CS+.
Conclusions: Our findings suggest a complex interaction between frontal and occipital cortex during cocaine conditioning. Frontal cortex is important for establishing novel representations of stimulus valence when cocaine is used as reinforcer, while early visual cortex is involved in retaining these cocaine-stimulus associations.