Hyperresponsiveness of the neural fear network during fear conditioning and extinction learning in male cocaine users

Objective: The authors investigated whether cocaine use disorder is associated with abnormalities in the neural underpinnings of aversive conditioning and extinction learning, as these processes may play an important role in the development and persistence of drug abuse. Method: Forty male regular cocaine users and 51 male control subjects underwent a fear conditioning and extinction protocol during functional MRI. Skin conductance response was measured throughout the experiment as an index of conditioned responses. Results: Cocaine users showed hyper responsiveness of the amygdala and insula during fear conditioning, as well as hyporesponsiveness of the dorsomedial prefrontal cortex during extinction learning. In cocaine users, but not in control subjects, skin conductance responses were positively correlated with responsiveness of the insula, amygdala, and dorsomedial prefrontal cortex during fear conditioning but negatively correlated with responsiveness of the ventromedial prefrontal cortex during extinction learning. Conclusions: Increased sensitivity to aversive conditioned cues in cocaine users might be a risk factor for stress-relief craving in cocaine use disorder. These results support the postulated role of altered aversive conditioning in cocaine use disorder and may be an important step in understanding the role of aversive learning in the pathology of cocaine use disorder.