Enduring changes in reward mechanisms after developmental exposure to cocaine: The role of the D2 receptor

During adolescent brain maturation, there are likely sensitive periods where environmental conditions, including drug exposure, may influence development by modifying neuronal connections. Altering neuronal function may produce different phenotypes than expected under normal conditions that may influence subsequent responding to drugs of abuse after the brain is fully mature. Experiment one investigated the relationship between novelty preference and cocaine place preference in adolescent and adult rats. High responding adolescent rats displaying greater free choice novelty exploration (but not forced novelty locomotion) expressed decreased cocaine place conditioning compared to low responding rats. No relationship was found in adult rats. Experiment two evaluated novelty-induced behaviors in adulthood after adolescent cocaine exposure. Repeated cocaine administration produced greater stress and anxiogenic behavioral responses to novelty in adult rats. Repeated alcohol administration produced less-inhibited novelty-induced behaviors in adulthood. Experiment three and four evaluated the consequence of developmental cocaine exposure on the rewarding efficacy of cocaine in adolescence and adulthood. Additionally, the interaction of D2 receptors and the rewarding efficacy of cocaine were investigated. After developmental cocaine exposure, adolescent and adult rats demonstrate decreased rewarding efficacy to cocaine. Importantly, blockade of the D2 receptor prevents cocaine-induced neurochemical changes, potentially regulating the behavioral and neurochemical alterations that occur after repeated drug use that increases the likelihood of dependence. Together, these data implicate both short and long-term behavioral adaptations that occur after developmental cocaine exposure that may result in a predisposition to develop adulthood drug dependence