An Examination of the Effects of Chronic Caffeine and Withdrawal from Chronic Caffeine on Fear Conditioning in Pre-adolescent, Adolescent, and Adult C57BL/6J Mice

Abstract

Caffeine is the most widely used psychoactive substance in the world. While findings suggest that chronic caffeine exerts negligible effects on cognition in adults, the effects of chronic caffeine on cognition in children and adolescents are not well understood. The hippocampus, a brain region important for learning and memory, undergoes extensive structural and functional modifications during pre-adolescence and adolescence. As a result, chronic caffeine may have differential effects on hippocampus-dependent learning and memory in pre-adolescents and adolescents compared to adults. The present study characterized the effects of chronic caffeine and withdrawal from chronic caffeine on hippocampus-dependent (contextual) and hippocampus-independent (cued) fear conditioning in pre-adolescent, adolescent, and adult mice. In addition, we investigated whether exposure to chronic caffeine during pre-adolescence, adolescence, or adulthood had long-lasting effects on conditioning in adulthood. Results indicate that exposure to chronic caffeine during pre-adolescence and adolescence either enhances or impairs contextual conditioning in a concentration-dependent manner. However, withdrawal from chronic caffeine impairs contextual conditioning in pre-adolescent mice only. In addition, exposure to chronic caffeine during pre-adolescence either enhances or impairs retention of contextual memories in adulthood in a concentration-dependent manner. In contrast, exposure to chronic caffeine during adolescence impairs cued conditioning in adulthood. These findings support the hypothesis that exposure to chronic caffeine during pre-adolescence and adolescence compromises hippocampus-dependent learning and memory. Furthermore, exposure to chronic caffeine during adolescence may produce long-lasting deficits in learning and memory in adulthood.