Adolescent alcohol consumption produces long term alterations in response inhibition and orbitofrontal-striatal activity in a sex-specific manner

Alcohol use disorder (AUD) is strongly associated with initiation of drinking during adolescence. Little is known about neural mechanisms that produce the long-term detrimental effects of adolescent drinking. A critical feature of AUD is deficits in response inhibition, or the ability to withhold a reward-seeking response. Here we sought to determine if adolescent drinking affects response inhibition and encoding of neural events by the orbitofrontal cortex (OFC) and dorsomedial striatum (DMS), two regions critical for expression of response inhibition. Adolescent male and female rats were given access to alcohol for four hours a day for five consecutive days. Then, rats were tested in a cued response inhibition task as adolescents or adults while we recorded concomitantly from the OFC and DMS. Adolescent voluntary alcohol drinking impaired response inhibition and increased alcohol drinking in adult male but not female rats. Adolescent alcohol drinking also resulted in sex-specific effects on both unit firing and local field potential measures in the OFC and DMS during premature and correct actions. Collectively, these data suggest sex-specific effects of adolescent alcohol drinking on response inhibition and corresponding alterations in cortical-striatal circuitry. HighlightsO_LIModerate adolescent alcohol drinking disrupts adult response inhibition C_LIO_LIAction encoding in the OFC and DMS changes after adolescent alcohol drinking C_LIO_LIOFC-DMS connectivity is altered in males after adolescent alcohol drinking C_LIO_LIAdolescent alcohol drinking promotes increased alcohol intake in adult males C_LI