The Role of Anterior Insular Parvalbumin GABAergic Interneurons in Impulsivity-Related and Alcohol-Seeking Behaviors

Abstract

Alcohol use is a major global health concern, particularly during adolescence, a developmental period characterized by heightened impulsivity, a known risk factor for alcohol misuse. The insular cortex is critically involved in interoceptive processing and impulsivity regulation, and its activity is powerfully shaped by parvalbumin (PV)-expressing GABAergic interneurons. We hypothesized that developmental differences in PV interneuron activity within the insular cortex contribute to impulsivity-related behaviors and alcohol consumption. To investigate this, male C57BL/6 mice were assessed at two developmental stages: adolescence (postnatal day 28) and young adulthood (postnatal day 64). Impulsivity was measured using the Omission-Contingency Learning (OCL) task, while alcohol intake and preference were evaluated using a two-bottle choice paradigm. Adolescent mice displayed higher impulsivity and greater alcohol consumption than adults. Double immunofluorescence labeling (Fos+/NeuN+ and Fos+/PV+) showed that increased impulsivity was associated with reduced activation of PV interneurons in the insular cortex. Chemogenetic activation of PV interneurons in adult PV-Cre mice reduced impulsivity in the OCL task and decreased alcohol intake. These findings indicate that insular PV interneurons play a modulatory role in impulsive behavior and alcohol consumption, suggesting a potential therapeutic target for impulse-control and alcohol-use disorders.