Effects of lowered serotonin transmission on cocaine-induced striatal dopamine response: PET [ 11C]raclopride study in humans

Abstract

Background: Low serotonin transmission is thought to increase susceptibility to a wide range of substance use disorders and impulsive traits. Aims: To investigate the effects of lowered serotonin on cocaineinduced (1.0 mg/kg cocaine, self-administered intranasally) dopamine responses and drug craving. Method: In non-dependent cocaine users, serotonin transmission was reduced using the acute tryptophan depletion method. Striatal dopamine responses were measured using positron emission tomography with [ 11C] raclopride. Results: Acute tryptophan depletion increased drug craving and striatal dopamine responses to cocaine. These acute tryptophan depletion-induced increases did not occur in the absence of cocaine. Conclusions: The results suggest that low serotonin transmission can increase dopaminergic and appetitive responses to cocaine. These findings might identify a mechanism by which individuals with low serotonin are at elevated risk for both substance use disorders and comorbid conditions. Declaration of interest: None.