A unique multi-synaptic mechanism involving acetylcholine and GABA regulates dopamine release in the nucleus accumbens through early adolescence in male rats

• Published in: eLife 2024-06, Vol.13
• Main Authors: Iacino, Melody C, Stowe, Taylor A, Pitts, Elizabeth G, Sexton, Lacey L, Macauley, Shannon L, Ferris, Mark J
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholine receptors (nicotinic); Adolescence; Adolescents; Adults; Behavior; Child development; Decision making; Dopamine; Females; GABA; Gender differences; Health aspects; Mediation; Mental disorders; Mental illness; Microdialysis; Neural transmission; Neurological research; nicotinic acetylcholine receptor; Nucleus accumbens; Phenols; Physiological aspects; Psychological aspects; Risk factors; Social aspects; Social behavior; Teenagers; Voltammetry; γ-Aminobutyric acid A receptors; γ-Aminobutyric acid B receptors
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.62999

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 associated behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry and microdialysis to examine differences in dopamine release as well as mechanisms that underlie differential dopamine signaling in the nucleus accumbens (NAc) core of adolescent (P28-35) and adult (P70-90) male rats. We show baseline differences between adult and adolescent stimulated dopamine release in male rats, as well as opposite effects of the a6 nicotinic acetylcholine receptor (nAChR) on modulating dopamine release. The a6-selective blocker, a-conotoxin, increased dopamine release in early adolescent rats, but decreased dopamine release in rats beginning in middle adolescence and extending through adulthood. Strikingly, blockade of GABA and GABA receptors revealed that this a6-mediated increase in adolescent dopamine release requires NAc GABA signaling to occur. We confirm the role of a6 nAChR and GABA in mediating this effect using microdialysis. Results herein suggest a multisynaptic mechanism potentially unique to the period of development that includes early adolescence, involving acetylcholine acting at a6-containing nAChRs to drive inhibitory GABA tone on dopamine release.