Cocaine self-administration behavior is associated with subcortical and cortical morphometry measures in individuals with cocaine use disorder.

Individual differences in gray-matter morphometry in the limbic system and frontal cortex have been linked to clinical features of cocaine use disorder (CUD). Self-administration paradigms can provide more direct measurements of the relationship between the regulation of cocaine use and gray-matter morphometry when compared to self-report assessments. Our goal was to investigate associations with self-administration behavior in subcortical and cortical brain regions. We hypothesized the number of cocaine infusions self-administered would be correlated with gray-matter volumes (GMVs) in the striatum, amygdala, and hippocampus. Due to scarcity in human studies, we did not hypothesize subcortical directionality. In the frontal cortex, we hypothesized thickness would be negatively correlated with self-administered cocaine. We conducted an analysis of cocaine self-administration and structural MRI data from 33 (n = 10) individuals with moderate-to-severe CUD. Self-administration lasted 60-minutes and cocaine (8, 16, or 32 mg/70 kg) was delivered on an FR1 schedule (5-minute lockout). Subcortical and cortical regression analyses were performed that included combined bilateral regions and age, experimental variables and use history as confounders. Self-administered cocaine infusions were positively associated with caudal GMV (b = 0.18,  = 0.030) and negatively with putamenal GMV (b = -0.10,  = 0.041). In the cortical model, infusions were positively associated with insular thickness (b = 0.39,  = 0.008) and women appeared to self-administer cocaine more frequently (b = 0.23,  = 0.019). Brain morphometry features in the striatum and insula may contribute to cocaine consumption in CUD. These differences in morphometry may reflect consequences of prolonged use, predisposed vulnerability, or other possibilities.Clinical Trial Numbers: NCT01978431; NCT03471182.