Abstract
ABSTRACT
Introduction/Aim
Adolescence is characterized by heightened impulsivity and increased vulnerability to alcohol misuse. The insular cortex is critically involved in impulse control, and parvalbumin‐expressing (PV) GABAergic interneurons strongly regulate its activity. We investigated whether developmental differences in insular PV interneuron activity contribute to impulsivity‐related behaviors and alcohol consumption.
Methods
Male C57BL/6 mice were assessed during adolescence (postnatal day 28) or young adulthood (postnatal day 64). Impulsivity was evaluated using the omission‐contingency learning (OCL) task, and alcohol intake and preference were measured using a two‐bottle choice paradigm with quinine adulteration. Neuronal activation in the insular cortex was analyzed using Fos immunolabeling combined with NeuN or PV markers. Chemogenetic manipulation of insular PV interneurons was performed in PV‐Cre mice.
Results
Adolescent mice exhibited greater impulsivity and higher alcohol consumption than adults. Although overall neuronal activation in the insular cortex was increased in adolescents, PV interneuron activation was reduced. Chemogenetic activation of insular PV interneurons decreased impulsive responding and alcohol intake, whereas inhibition produced the opposite effects.
Conclusion
Insular PV interneurons exert critical control over impulsivity and alcohol‐seeking behaviors. Developmental differences in PV‐mediated inhibitory regulation within the insular cortex may underlie adolescent vulnerability to alcohol misuse.