Moderate adolescent chronic intermittent ethanol exposure sex-dependently disrupts synaptic transmission and kappa opioid receptor function in the basolateral amygdala of adult rats

Adolescent alcohol exposure is associated with many consequences in adulthood, including altered affective and reward-related behaviors. However, the long-term neurological disruptions underlying these behaviors are not fully understood. Shifts in the excitatory/inhibitory balance in the basolateral amygdala (BLA) relate to the expression of these behaviors and changes to BLA physiology are seen during withdrawal immediately following adolescent ethanol exposure, but no studies have examined whether these changes persist long-term. The kappa opioid receptor (KOR) neuromodulatory system mediates negative affective behaviors, and alterations of this system are implicated in behavioral changes following adult and adolescent chronic ethanol exposure. In the BLA, the KOR system undergoes functional changes across development, but whether BLA KOR function is disrupted by adolescent ethanol exposure is unknown. In this study, male and female Sprague-Dawley rats were exposed to a vapor model of moderate adolescent chronic intermittent ethanol (aCIE) and assessed for long-term effects on GABAergic and glutamatergic neurotransmission within the adult BLA and KOR modulation of these systems. aCIE exposure increased presynaptic glutamate transmission in females but had no effect in males or on GABA transmission in either sex. Additionally, aCIE exposure disrupted male KOR modulation of GABA release, with no effects in females or on glutamate transmission. These data suggest that aCIE produces sex-dependent and long-term changes to BLA physiology and KOR function. This is the first study to examine these persistent adaptations following adolescent alcohol exposure and opens a broad avenue for future investigation into other adolescent ethanol-induced disruptions of these systems.

Automated summary

The study reveals that adolescent alcohol exposure may result in long-term sex-dependent effects on BLA physiology and KOR function in adulthood, impacting the modulation of GABAergic and glutamatergic neurotransmission.