Impact of Age and Prior History of Ethanol Exposure on Ethanol-Induced Patterns of Neuronal Activation in cFos-LacZ Adolescent Male and Female Rats

Abstract

Adolescent binge alcohol alters late-developing brain regions and increases the risk for long-term reward, cognitive, and emotional dysregulation. Adolescent intermittent ethanol (AIE) exposure in rodents produces similar behavioral alterations into adulthood, but the effects of acute high-dose ethanol on patterns of neuronal activation in late developing brain regions remain poorly understood. In the current study, adolescent male and female cFos-LacZ rats were acutely challenged with water or 4 g/kg ethanol intragastrically (IG) on postnatal day (P) 25 or P45, early- and late-adolescence, with brains collected 1 h later. P45 rats with a history of water or AIE (10 exposures every other day from P25 to P45) were included as a chronic exposure condition. β-galactosidase expression was used as a proxy for Fos neuronal activation. Acute IG gavage increased neuronal activation in multiple brain regions irrespective of water or ethanol challenge, and increases were attenuated by adolescent chronic exposure. Increased neuronal activation was evident only in the central amygdala (CeA) after acute ethanol challenge, with this effect being attenuated by AIE. Functional network mapping revealed age-, sex-, and exposure-related differences: water-exposed adolescent males had salient network hub regions, while control females had age-related transitions from salient to executive control network regions. Ethanol disrupted these trajectories. In males, acute ethanol reduced functional network connectivity, with chronic ethanol decentralizing hubs. In females, ethanol enhanced connectivity centered on the nucleus accumbens. These findings highlight the CeA as an ethanol-sensitive region across sexes, but reveal sex differences in adolescent ethanol exposure on functional networks.