Comparing dopamine release, uptake, and D2 autoreceptor function across the ventromedial to dorsolateral striatum in adolescent and adult rats

Abstract

Adolescents have increased vulnerability for the development of a range of psychiatric disorders, including substance abuse disorders (SUD) and mood disorders. Adolescents also have increased rates of sensation seeking and risk taking. The mesolimbic dopamine system plays a role in all these behaviors and disorders and reorganization of the dopamine system during adolescence may be important in mediating these developmental changes in behavior and vulnerability. Here, we used ex vivo fast scan cyclic voltammetry to examine developmental differences in dopamine release and its local circuitry regulation across the striatum. We found that adolescents have significantly decreased dopamine release in the nucleus accumbens core across a range of stimulation frequencies that model tonic and phasic firing of mesolimbic dopamine neurons. We show this is not mediated by differences in rate of dopamine uptake, but may be driven by hypersensitive dopamine autoreceptors, indicated by increased inhibition in dopamine release following agonism of D2/D3 receptors, in the adolescent nucleus accumbens core. Additionally, we observed increases in dopamine uptake in the dorsomedial striatum. No other significant differences between release, uptake, or D2 autoreceptor function was observed between adolescent and adult rats in all brain areas tested (nucleus accumbens shell, nucleus accumbens core, dorsomedial striatum, and dorsolateral striatum). These developmental differences in dopamine release may be important in mediating some of the unique behavioral repertoire seen in adolescents, such as increases in sensation seeking, and its associated vulnerabilities.