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

Bezerra, F.; Fernandes, G. J. D.; Anjos-Santos, A.; Favoreto, C. A.; Rodolpho, B. T.; Palombo, P.; Belujon, P.; Vialou, V.; Abrahao, K. P.; Cruz, F.

doi:10.64898/2025.12.15.694283

bioRxiv · 10.64898/2025.12.15.694283

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

Bezerra, F.·Fernandes, G. J. D.·Anjos-Santos, A.·Favoreto, C. A.·Rodolpho, B. T.·Palombo, P.·Belujon, P.·Vialou, V.·Abrahao, K. P.·Cruz, F.

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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.

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Bezerra, F., Fernandes, G. J. D., Anjos-Santos, A., Favoreto, C. A., Rodolpho, B. T., Palombo, P., Belujon, P., Vialou, V., Abrahao, K. P., Cruz, F.. 2025-12-16. The Role of Insular Anterior Parvalbumin GABAergic Interneurons in Impulsivity-Related and Alcohol-Seeking Behaviors. https://doi.org/10.64898/2025.12.15.694283

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