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bioRxiv · 10.64898/2026.06.05.730464

Dynorphinergic neuroadaptations in the islands of Calleja: implications for alcohol use disorder

Cuozzo, A. M.·Lepreux, G.·Reis, D. J.·Wei, G.·Walker, B. M.
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Abstract

Dysregulation of the dynorphin (DYN) / kappa-opioid receptor (KOR) system is heavily implicated in symptoms of alcohol use disorder (AUD) including negative affective-like states that can drive maladaptive behavioral regulation. Substantial efforts have been made towards understanding the neurobiology of DYN / KOR dysregulation; however, the role of dynorphinergic islands of Calleja within the ventral striatum remain poorly understood. Presently, adult male Wistar rats were trained to self-administer 10% alcohol, exposed to either air or alcohol vapor for eight weeks, and alcohol self-administration and 22-kHz ultrasonic vocalizations (USVs) assessed during acute withdrawal. Subsequently, brains were extracted during acute withdrawal and DYN A-like immunoreactivity was measured in the ventral striatum. Alcohol vapor-exposed rats demonstrated increased alcohol consumption and 22-kHz USVs compared to air-exposed controls. Vapor-exposed rats additionally demonstrated increased DYN A-like immunoreactivity in the islands of Calleja. Moreover, the average DYN A neuron size positively correlated with the number of 22-kHz USVs in vapor exposed animals, but not in air-exposed controls. The present findings identify the islands of Calleja as a novel DYN-associated region that may be recruited during alcohol dependence with enhanced DYN plasticity in the islands of Calleja contributing to affective dysregulation in AUD and other neuropsychiatric conditions.

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Cuozzo, A. M., Lepreux, G., Reis, D. J., Wei, G., Walker, B. M.. 2026-06-10. Dynorphinergic neuroadaptations in the islands of Calleja: implications for alcohol use disorder. https://doi.org/10.64898/2026.06.05.730464

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