Enhanced behavioral response to repeated-dose cocaine in adolescent rats

Rationale: Most lifelong drug addiction in humans originates during adolescence. Important structural and functional changes in the brain occur during adolescence, but there has been little direct study of how this impacts on drug abuse vulnerability. An emerging literature suggests that adolescents exhibit different behavioral responses to single doses of several addictive drugs, including ethanol, amphetamine, and cocaine. However, few studies have explored behavioral responses to the repeated dosing that is characteristic of human abuse of these substances. Objectives: We have investigated age-related behavioral responses to acute "binge" cocaine treatment between adults and adolescents. Results: Adolescent rats displayed an exaggerated behavioral response to cocaine administered in two different binge patterns. Total locomotion after cocaine administration was the same in adolescents and adults. However, adolescent rats engaged in more intense stereotypic behaviors, including paw treading, head weaving, and focused sniffing than adult rats. These differences were observable following a modest dose of cocaine and became more robust following subsequent doses within a binge. Cocaine blood and brain levels were not significantly different between age groups during any of the exposure sessions. Conclusions: These findings suggest that equivalent tissue concentrations of cocaine produce a greater behavioral response in young rats, and that adolescent animals display an apparent form of intrabinge sensitization.