Adolescent-onset vs. adult-onset cocaine use: Impact on cognitive functioning in animal models and opportunities for translation.

Animal models are poised to make key contributions to the study of cognitive deficits associated with chronic cocaine use in people. Advantages of animal models include use of a longitudinal experimental design that can control for drug use history and onset-age, sex, drug consumption, and abstinence duration. Twenty-two studies were reviewed (13 in adult male rats, 5 in adolescent vs. adult male rats, 3 in adult male monkeys, and 1 in adult female monkeys), and it was demonstrated repeatedly that male animals with adult-onset cocaine self-administration exposure had impairments in sustained attention, decision making, stimulus-reward learning, working memory, and cognitive flexibility, but not habit learning and spatial learning and memory. These findings have translational relevance because adult cocaine users exhibit a similar range of cognitive deficits. In the limited number of studies available, male rats self-administering cocaine during adolescence were less susceptible than adults to impairment in cognitive flexibility, stimulus-reward learning, and decision making, but were more susceptible than adults to impairment in working memory, a finding also reported in the few studies performed in early-onset cocaine users. These findings suggest that animal models can help fill an unmet need for investigating important but yet-to-be-fully-addressed research questions in people. Research priorities include further investigation of differences between adolescents and adults as well as between males and females following chronic cocaine self-administration. A comprehensive understanding of the broad range of cognitive consequences of chronic cocaine use and the role of developmental plasticity can be of value for improving neuropsychological recovery efforts.