Acute methylphenidate administration reduces cocaine-cue attentional bias

Abstract

Mechanistic research on behavioral processes underlying substance use disorder might help identify novel targets for interventions development. Drug-related attentional bias and response inhibition deficits have received a great deal of consideration in substance use research, broadly, and cocaine use research, specifically. Studies investigating pharmacological mechanisms that may ameliorate, or further impair, these behaviors relevant to cocaine use are relatively lacking. This study evaluated the impact of acute administration of methylphenidate, a dopamine-favoring reuptake inhibitor, on both gaze-related cocaine-cue-attentional bias and cocaine-cue related disruptions in response inhibition among individuals with cocaine use disorder. Participants (N = 12; 33% female) completed a within-subject, outpatient, acute dosing study. Two sessions were completed in which methylphenidate (60 mg) or placebo were administered followed by completion of an attentional bias task using eye-tracking technology and neutral-cue and cocaine-cue response inhibition tasks. Subjective and physiological effects were also recorded. Significant cocaine cue attentional bias and response inhibition failures were observed during placebo administration. Acute methylphenidate administration reduced cocaine-cue attentional bias as measured by cocaine-cue gaze fixations (d_z = 1.04; Bayes Factor = 12.37). No statistically significant effects of methylphenidate were observed on response inhibition (Bayes Factors = 0.17-1.04). Methylphenidate produced prototypical subjective and physiological effects. Although the small sample should be considered, these findings indicate acute manipulation of dopaminergic activity reduced cue-related attentional allocation related to cocaine use disorder. Future research evaluating alternative dopaminergic agents and applications within a clinical setting are needed to determine the clinical significance of targeting this neurobehavioral mechanism.

Keywords: Attention; Behavior; Eye-tracking; Inhibitory control; Response inhibition.