ADOLESCENT ALCOHOL EXPOSURE ALTERS ADULT STRESS-INDUCED VOCALIZATIONS IN MICE: PROTECTIVE EFFECTS OF DHA SUPPLEMENTATION

Adolescence is a period of increased risk-taking behavior, including alcohol and drug abuse. Alcohol exposure during this period enhances anxiety-like behavior and increases the risk of developing an alcohol use disorder (AUD) in adulthood. Omega-3 polyunsaturated fatty acids (n-3 PUFAs), specifically docohexaenoic acid (DHA), exhibit neuroprotective properties and may mitigate alcohol-induced synaptic deficits and anxiety. Recently, ultrasonic vocalizations (USVs) have emerged as reliable biomarkers of emotional states in rodents, with specific frequency shifts reflecting anxiety levels. The study evaluated the effect of DHA on USVs during acute stress in adult mice exposed to heavy alcohol consumption during adolescence. Male mice underwent a 4-week “Drinking-in-the-Dark” protocol (PND 32–60). Subsequently, subjects received either DHA-enriched fish oil (700 mg/kg) via gavage three times weekly for 8 weeks. At PND118, vocalizations were obtained by placing the mouse in a narrow tube inside a soundproof box for a period of 10 minutes. The results showed that the total number of vocalizations emitted was consistent across all groups. However, the percentage of mid-frequency vocalizations (MFVs) emitted by the pre-exposure ethanol group was higher than that emitted by the water-control group. Interestingly, DHA supplementation significantly reduced the percentage of low-frequency vocalizations (LFVs). Adolescent alcohol exposure induces long-term changes in vocalization patterns,that reflect altered emotional processing in adulthood. The modulation of specific USVs frequencies by DHA suggests an anxiolytic effect, supporting its potential as a nutritional intervention for alcohol-related emotional dysregulation(This work was supported by the Grant PID2021-128650NA-I00 funded by MCIN/AEI/ 10.13039/501100011033; PPIT-UAL, Junta de Andalucía-ERDF 2021-2027).