The first experience most people have with addictive drugs occurs during adolescence and addiction may develop more quickly during adolescence than later in life. The present proposal tests the hypothesis that maturational events in presynaptic dopamine mechanisms contribute to the altered biologic reactivity of adolescents to behavioral and pharmacological stimuli. It is based on preliminary data showing greater baseline dopamine uptake, enhanced dopamine responses to cocaine and enhanced behavioral responses to cocaine in adolescent (day 28) compared to young adult (60 day old) rats. We will test this hypothesis by evaluating dopamine terminal function and dopamine responses to behavioral stimuli and drugs through adolescence. We will evaluate dopamine uptake and release through adolescence in male and female rats using both fast scan cyclic voltammetry (FSCV) in awake, behaving animals, and using in vitro preparations. First, we will determine the contribution of synaptosomal and vesicular uptake to the enhanced uptake observed in vivo. Second, we will determine the kinetics of dopamine uptake and release at baseline and after cocaine and L-Dopa using FSCV in 28, 42, 60 and 90 day old intact behaving male and female rats. Third, we will determine dopamine responses to an environmental stimulus (voluntary exposure to a novel environment) using FSCV in awake behaving animals. These studies should provide insight into potential biologic mechanisms that influence the onset of drug taking during adolescence.
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