Adolescents differ from adults in cocaine conditioned place preference and cocaine-induced dopamine in the nucleus accumbens septi

In humans, adolescent exposure to illicit drugs predicts the onset of adult drug abuse and suggests that early drug use potentiates vulnerability to drug addiction. Cocaine conditioned place preferences were measured in early adolescent [postnatal day (PND) 35], late adolescent (PND 45) and young adult (PND 60) rats by injecting either 0, 5 or 20 mg/kg cocaine and conditioning them to environmental cues. Cocaine preferences were found for all ages at the high dose. PND 35s were the only age group to have a preference at the low dose. To address whether age-related differences in cocaine place preferences were related to differences in the mesolimbic dopaminergic system, we measured extracellular dopamine levels in the nucleus accumbens septi of PND 35, PND 45 and PND 60 rats via quantitative microdialysis under transient conditions. Rats were injected daily with either 5 mg/kg/ip or saline for 4 days and surgically implanted with a microdialysis probe aimed at the nucleus accumbens. Rats were perfused with either 0, 1, 10 or 40 nM dopamine and the extracellular dopamine concentration was measured. Our results show that adolescents differ from adults in basal dopamine. All cocaine treated rats, regardless of age, showed a significant increase in dopamine over baseline in response to a cocaine challenge. Additionally, there were age-related differences in the extraction fraction (E-d), an indirect measure of dopamine reuptake. Together these findings suggest ontogenetic differences in extracellular dopamine and dopamine reuptake and that these differences may provide an explanation for adolescent vulnerability to addiction. (c) 2006 Elsevier B.V. All rights reserved.