IDENTIFYING BEHAVIORAL AND BIOLOGICAL PREDICTORS OF CANNABIS VAPOR SELF-ADMINISTRATION IN FEMALE AND MALE RATS
Creators: name: Park, Ginny I.
Publisher: name: Washington State University
Year: 2024
Subjects: Animal Model
Cannabis
Cannabis Use Disorder
Research Domain Criteria
Self-Administration

description: Approximately 9% of first-time cannabis users will become dependent on cannabis, yet there are no FDA-approved pharmacotherapies for managing cannabis use disorder (CUD). This is in part due to flawed diagnostic nosology resulting in a lack of understanding of the mechanisms that give rise to CUD, as well as a conspicuous lack of translationally relevant animal models of cannabis use. To address these gaps, we have developed a model of cannabis self-administration that delivers vaporized cannabis extract in a response-contingent manner via the pulmonary route of administration that is most common in humans. We used this model to identify behavioral and biological predictors of motivation to self-administer vaporized cannabis in rats. We conducted an extensive battery of behavioral assays in female and male Long Evans rats (N=48) prior to initiation of cannabis self-administration training and characterized endophenotypes using endpoints that correspond to the behavioral dimensions of the NIMH Research Domain Criteria (RDoC). We then used a series of linear regression analyses to determine whether behavioral and physiological parameters in the five RDoC dimensions (positive and negative valence systems, cognition, social processes, and arousal/regulatory systems) significantly predicted the number of cannabis vapor deliveries earned during a 3-hr progressive ratio test after four weeks of cannabis self-administration. The Positive Valence model was significant, accounting for 21.1% of the variance in cannabis self-administration, with greater motivation for sucrose reinforcement predicting higher rates of cannabis self-administration (p=.008). The Cognition model was significant, accounting for 17.9% of the variance in cannabis self-administration. Specifically, better visual cue discrimination and poorer set shifting performance each predicted higher rates of cannabis self-administration (p’s = .015 and .030, respectively). The Arousal/Regulatory Systems model was also significant, accounting for 59.3% of the variance in cannabis self-administration. Specifically, higher concentrations of basal corticosterone (CORT) predicted higher rates of cannabis vapor self-administration (p = .005), while lower concentrations of plasma anandamide (AEA) content predicted higher rates of self-administration (p = .008). Finally, the Social Processes and Negative Valence models were not significant predictors of cannabis self-administration. Our data indicate that basal CORT, circulating AEA content, high motivation for sucrose reinforcement, and greater reliance on visual cue-based strategies were all significant predictors of motivation to self-administer cannabis vapor in adulthood. Thus, these endophenotypes may precede the onset of problematic cannabis use, which could be leveraged to identify individuals with increased susceptibility for developing CUD.