Development of working memory in the male adolescent rat

Working memory develops over the course of adolescence, and neuroimaging studies find development-associated changes in the activity of prefrontal cortical brain regions. Establishment of a rodent model of working memory development would permit more comprehensive studies of the molecular and circuit basis for working memory development in health and disease. Thus, in this study, working memory performance was compared between adolescent and adult male Sprague-Dawley rats using an operant-based, delay-match-to-sample working memory task. Adolescent and adult rats showed similar rates of learning the task and similar performance at a low cognitive load (delays ≤ 6 s). However, when the cognitive load increased, adolescents exhibited impaired working memory performance relative to adults, until postnatal day 50 when performance was not significantly different. Despite evidence that cannabinoids disrupt working memory, we found no effect of acute treatment with the cannabinoid receptor agonist, WIN55212,2, at either age. Moreover, expression of glutamate and GABA receptor subunits was examined in the prelimbic and infralimbic prefrontal cortex across development. NMDA receptor subunit GluN2B expression significantly decreased with age in parallel with improvements in working memory. Thus, we show evidence that rats can be used as a model to study the molecular underpinnings of working memory development.