Impaired Synaptic Activity in the Basolateral Amygdala Is Associated With an Alcohol Use Disorder-Like Vulnerable Phenotype in Male Rats.

Alcohol use disorder (AUD) is associated with a loss of control over alcohol use, putatively driven by maladaptive changes in neural circuitries, including the basolateral amygdala (BLA). The BLA, known for its role in emotional regulation and associative learning, contributes to the reinforcement of alcohol-related behaviours, making it a critical target for understanding the underlying mechanisms of vulnerability to AUD. To further outline the role of BLA neurotransmission in AUD, we combined a multisymptomatic 0/3 criteria rodent model with electrophysiological whole-cell recordings to identify the association between neurophysiological parameters in the BLA and vulnerability to AUD-like progression. Our results demonstrate that when assessed after 4 months of voluntary alcohol consumption, rats can be subcategorized as resilient or vulnerable to AUD-like behaviour. Electrophysiological recordings, performed directly after alcohol self-administration, demonstrated that rats manifesting an AUD-like vulnerable phenotype presented a reduced frequency and amplitude of spontaneous excitatory post-synaptic currents (sEPSCs), indicating suppressed activation via glutamatergic inputs. Disinhibition induced by GABAA receptor antagonist did not differ between groups, and field potential recordings demonstrated reduced stimulus/response curves further supporting a hypoglutamatergic state. Additionally, the intrinsic excitability of BLA neurons was selectively decreased in vulnerable rats compared to both resilient and water control rats. Importantly, addiction score correlated with both synaptic transmission and intrinsic excitability of BLA neurons. Overall, our findings suggest that hypoexcitability of BLA neurons may represent a neurobiological underpinning that contributes to the development and persistence of alcohol addiction-like behaviours following protracted alcohol exposure.