Are cocaine users too sensitive? Functional and structural brain imaging studies in regular cocaine users

While previous research primarily focused on the involvement of the frontostriatal network in the etiology of substance use disorder, it has recently been suggested that the amygdala, and its interaction with the frontostriatal circuitry, may play a key role in habitual drug seeking, and therefore in the etiology of substance use disorder The studies described in this dissertation demonstrate that cocaine use disorder is associated with hyper-activity of the amygdala in response to negative emotional facial expression, cocaine-related stimuli and fear-conditioned stimuli. Furthermore, we demonstrated that childhood adversity disrupts amygdala-ventral striatal coupling during cocaine cue-exposure, whereas state anxiety disrupts amygdala-prefrontal cortex coupling during cocaine cue-exposure. In addition, we demonstrated that trait impulsivity and the degree of polysubstance use selectively alters prefrontal cortex structure. Finally, in healthy, non-drug using individuals we demonstrated that anticipation of a negative outcome reduces reward reinstatement in the ventral striatum.
Based on these findings I propose a model of the involvement of the amygdala-ventral striatal-prefrontal cortex circuitry in cocaine use disorder: In this model, impaired amygdala-ventral striatal coupling in cocaine users is suggested to be related to childhood adversities and to predispose to compulsive behavior. In addition, impaired amygdala-prefrontal cortex coupling is suggested to be related to impulsivity and polysubstance use and to predispose to impaired emotion regulation. Using this model we hope to increase to knowledge on the role of the amygdala and its interaction with the frontostriatal system in substance use disorder, which may contribute to improve treatment outcome in those that are currently treatment-resistant.