Relationship between cognitive performance and social rank in male and female cynomolgus macaques: Implications for the role of cognition in vulnerability to cocaine use disorder

Abstract

Cocaine use disorder (CUD) currently has no FDA-approved pharmacological treatment. One of the most promising behavioral interventions is cognitive behavioral therapy. Still, there is a continuing need to understanding what makes an individual susceptible to CUD. A major goal of this study is to determine if cognitive performance can serve as a behavioral biomarker related to vulnerability to cocaine abuse. Previous studies have shown sex differences in vulnerability to cocaine based on social rank (Morgan et al., 2002; Nader et al., 2012). The goal of the present study is to evaluate cognitive performance as a potential biomarker for vulnerability to cocaine abuse, in socially housed cocaine-naïve female and male monkeys. In an earlier study involving newly formed social groups of female monkeys, performance on one cognitive domain, working memory using a delayed-match-to-sample task, showed social rank differences only during establishment of the social hierarchy; once the hierarchies were stable, there were no differences in working memory across social ranks (Kromrey et al., 2016). The present study differs from our earlier work by studying several cognitive domains in well-established, same-sex, male and female social groups (N=8/sex). Monkeys were trained to complete a battery of cognitive tasks which evaluated learning and memory (stimulus discrimination; SD and compound discrimination; CD), executive function (reversal learning; SDR) and behavioral flexibility (interdimensional shifting; ID, extradimensional shifting; and reversal, ED, EDR). The test battery consisted of monkeys performing all tasks (SD/SDR, CD, ID, ED/EDR) in 1-3 sessions; criteria for moving to the next task was 12/15 trials correct. All studies were performed in accordance with the FASEB Statement of Principles for the Use of Vertebrate Animals in Research and Education and Wake Forest's IACUC. We hypothesized that because earlier work had shown subordinate males and dominant females were more vulnerable to cocaine reinforcement, that they would show poorer cognitive performance relative to dominant males and subordinate females. In preliminary findings, dominant male and female monkeys made fewer total errors and required less trials to complete the battery compared with subordinate animals, in contrast to our hypothesis. Next, acquisition of cocaine reinforcement will be examined in an effort to replicate earlier findings and then the test battery will be repeated at various timepoints in order to evaluate the effects of cocaine on cognitive performance as a function of sex and social rank.