Walker, C. D. | Search bioRxiv

bioRxiv2025

Adolescent Alcohol Exposure Disrupts Astrocyte-Synaptic Structural And Functional Coupling In The Male Dorsal Hippocampus

Adolescence is a window of heightened vulnerability to the neurotoxic effects of binge ethanol exposure. Adolescent intermittent ethanol (AIE) exposure has been shown to induce long-lasting cognitive and behavioral impairments in patients and rodent models that increase the risk of developing alcohol use disorder (AUD). Our previous work shows that these behavioral deficits coincide with persistent astrocyte dysfunction. Here, we aim to understand how astrocyte-synaptic structural and functional crosstalk are disrupted following AIE to provide better mechanistic understanding of why behavioral impairments persist into adulthood. Male Sprague-Dawley rats received AIE, a variety of adeno-associated viruses encoding astrocyte-specific sensors, and fiber implantation in the dorsal hippocampal (dHipp) for in vivo photometry. A subset of rats received hM3D(Gq) to chemogenetically activate astrocytes. Following AIE and a forced abstinence period that allowed growth into adulthood, rats underwent assessment in the contextual fear conditioning (CFC) task with simultaneous fiber photometry recordings. By combining immunohistochemistry (IHC), Stimulated Emission Depletion (STED) microscopy, fiber photometry, chemogenetics, and slice physiology, we show that AIE induces structural and functional decoupling of astrocytes from synapses and astrocyte dysregulation that persists into adulthood. Remarkably, stimulating astrocytic calcium signaling via chemogenetic activation partially attenuates heightened fear responding and increases gliotransmitter availability. These findings highlight a critical role for astrocyte-synaptic crosstalk in regulating fear learning and underscore the untapped therapeutic potential of targeting astrocytes to improve behavioral outcomes following substance use.

neuroscience↗

bioRxiv2020

Investigating the sex-specific effects of socialization on voluntary ethanol self-administration in rats using an eVape system

IntroductionAdolescence is characterized as a transitional developmental period between childhood and adulthood that is associated with increased freedom and novel experiences that are frequently peer-influenced. Due to newfound independence, there is a higher prevalence of alcohol consumption, which is heightened by the rewarding effects of alcohol. However, the contributions of social interaction and sexual dimorphism to alcohol intake are not fully understood. Here we explore the use a novel self-administration ethanol (EtOH) vapor system to investigate the sexual dimorphic nature of socially facilitated ethanol exposure. MethodsAdolescent and adult male and female Sprague-Dawley rats underwent a novel voluntary intermittent EtOH vapor paradigm. Nosepoke initiated self-administration vapor chambers administered 20mg/L of vaporized EtOH or air into the chamber following each nosepoke. Beginning on postnatal day 30 (PND30), during the onset of adolescence, or 70 (PND70), at the onset of adulthood, animals were placed in vapor chambers for 4hr every other day for 40 sessions. All animals underwent 10 sessions with their cagemate (social access) followed by 10 sessions in isolation (isolated access), a 10-day forced abstinence period, 10 sessions isolated access, and 10 sessions social access. ResultsThese data reveal that despite low EtOH consumption across all groups, adolescent (PND30) and adult (PND70) female rats voluntarily self-administered more EtOH vapor per body weight than age-matched males, while male rats increased EtOH preference over sessions regardless of age. In addition, all rats regardless of sex or age voluntarily self-administered more EtOH vapor per body weight during the social access session than during the subsequent isolated access sessions. ConclusionThese data demonstrate that under these experimental parameters, male and female rats regardless of age do not self-administer high quantities of EtOH vapor using this paradigm. Further work is required to determine whether the nose-poke EtOH vapor self-administration apparatus can be modified to promote high voluntary EtOH consumption that can be socially facilitated. These data demonstrate that with further investigation, the self-administration EtOH vapor system could be an effective alternative to other methods of voluntary EtOH administration to further our understanding of socially facilitated drinking.

neuroscience↗