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

ABSTRACT

Background: 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.

Objectives: 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.

Methods: We conducted an analysis of cocaine self-administration and structural MRI data from 33 (n_Females = 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.

Results: Self-administered cocaine infusions were positively associated with caudal GMV (b = 0.18, p = 0.030) and negatively with putamenal GMV (b = −0.10, p = 0.041). In the cortical model, infusions were positively associated with insular thickness (b = 0.39, p = 0.008) and women appeared to self-administer cocaine more frequently (b = 0.23, p = 0.019).

Conclusions: 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

KEYWORDS:

• Addictive behaviors
• cocaine use disorder
• impulsive behavior
• compulsive behavior
• brain morphometry
• MRI

Acknowledgments

It is with significant sadness that we note the passing of Dr Robert T. Malison in July of 2020. Dr Malison made many important contributions to the field of cocaine use disorder research and addiction research more generally. He was Investigator or Principal Investigator on grants providing data for this work as well as sponsor of IND required for human laboratory cocaine self-administration paradigms. As such, this manuscript would not have been feasible without him. We would like to thank the staff of the Clinical Neuroscience Research Unit at the Connecticut Mental Health Center and the Hospital Research Unit at Yale New-Haven Hospital.

We also acknowledge contributions from former team members of Yale Cocaine Research Clinic (i.e., Jessica Costeines and Benjamin Kazer) as well as collaborators (i.e., Dr. David Matuskey) on obtaining and organization of data from original source documents.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/00952990.2024.2318585

Additional information

Funding

Supported through NIH R01DA052454 (GAA), R21DA040914 (GAA), T32DA007238 and U54AA027989] (RK), P20DA027844 (MNP), K01DA042998 (PDW). R03DA027456 and R03DA025176 (Robert T. Malison; not listed as author given his untimely passing prior to the initiation of the manuscript). The work described in this article was funded in part by the State of Connecticut, Department of Mental Health and Addiction Services. This publication does not express the views of the Department of Mental Health and Addiction Services or the State of Connecticut. The views and opinions expressed are those of the authors.