Saddoris, M. P. | bioRxiv Science

bioRxiv2023

Voluntary alcohol consumption during distinct phases of adolescence differentially alters adult fear acquisition, extinction and renewal in male and female rats

Alcohol use during adolescence coincides with elevated risks of stress-related impairment in adults, particularly via disrupted developmental trajectories of vulnerable corticolimbic and mesolimbic systems involved in fear processing. Prior work has investigated the impact of binge-like alcohol consumption on adult fear and stress, but less is known about whether voluntarily consumed alcohol imparts differential effects based on adolescence phases and biological sex. Here, adolescent male and female Long Evans rats were granted daily access to alcohol (15%) during either early (Early-EtOH; P25-45) or late adolescence (Late-EtOH; P45-55) using a modified drinking-in-the-dark design. Upon adulthood (P75-80), rats were exposed to a three-context (ABC) fear renewal procedure. We found that male and female Early-EtOH rats showed faster acquisition of fear but less freezing during early phases of extinction and throughout fear renewal. In the extinction period specifically, Early-EtOH rats showed normal levels of freezing in the presence of fear-associated cues, but abnormally low freezing immediately after cue offset, suggesting a key disruption in contextual processing and/or novelty seeking brought by early adolescent binge consumption. While the effects of alcohol were most pronounced in the Early-EtOH rats (particularly in females), Late-EtOH rats displayed some changes in fear behavior including slower fear acquisition, faster extinction, and reduced renewal compared with controls, but primarily in males. Our results suggest that early adolescence in males and females and, to a lesser extent, late adolescence in males is a particularly vulnerable period wherein alcohol use can promote stress-related dysfunction in adulthood. Furthermore, our results provide multiple bases for future research focused on developmental correlates of alcohol mediated disruption in the brain.

neuroscience↗

bioRxiv2021

Elevated fear responses to threatening cues in rats with early life stress is associated with greater excitability and loss of gamma oscillations in ventral-medial prefrontal cortex

Stress experienced early in development can have profound influences on developmental trajectories and ultimately behaviors in adulthood. Potent stressors during brain maturation can profoundly disrupt prefrontal cortical areas in particular, which can set the stage for prefrontal-dependent alterations in fear regulation and risk of drug abuse in adulthood. Despite these observations, few studies have investigated in vivo signaling in prefrontal signals in animals with a history of early life stress (ELS). Here, rats with ELS experienced during the first post-natal week were then tested on a conditioned suppression paradigm during adulthood. During conditioned suppression, electrophysiological recordings were made in the ventral medial prefrontal cortex (vmPFC) during presentations of a fear-associated cues that resolved both single-unit activity and local field potentials (LFPs). Relative to unstressed controls, ELS-experienced rats showed greater fear-related suppression of lever pressing. During presentations of the fear-associated cue (CS+), neurons in the vmPFC of ELS animals showed a significant increase in the probability of excitatory encoding relative to controls, and excitatory phasic responses in the ELS animals were reliably of higher magnitude than Controls. In contrast, vmPFC neurons in ELS subjects better discriminated between the shock-associated CS+ and the neutral ("safe") CS-cue than Controls. LFPs recorded in the same locations revealed that high gamma band (65-95 Hz) oscillations were strongly potentiated in Controls during presentation of the fear-associated CS+ cue, but this potentiation was abolished in ELS subjects. Notably, no other LFP spectra differed between ELS and Controls for either the CS+ or CS-. Collectively, these data suggest that ELS experience alters the neurobehavioral functions of PFC in adulthood that are critical for processing fear regulation. As such, these alterations may also provide insight into to increased susceptibility to other PFC-dependent processes such as risk-based choice, motivation, and regulation of drug use and relapse in ELS populations.

neuroscience↗