A unique multi-synaptic mechanism regulates dopamine release in the nucleus accumbens during adolescence

Summary Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry to examine differences in regulation of dopamine release in the nucleus accumbens core of adolescent and adult male rats. We found that differences between adolescent and adult stimulated dopamine release is driven by a unique multisynaptic mechanism in early adolescence involving acetylcholine acting at α6-containing nicotinic acetylcholine receptors to mediate inhibition of dopamine via GABA release. These changes in dopamine regulation across adolescence provides a springboard for our understanding of basic brain development and targeted therapy for a range of psychiatric conditions that emerge in adolescence.