Sex differences in ethanol-induced inhibition of hyperpolarization-activated current and excitability of amygdala neurons after traumatic stress.

The basolateral amygdala (BLA) plays a vital role in integrating sensory information and establishing emotional salience of the environment. Ethanol potentiates GABAergic inhibition in BLA neurons, regulating excitatory transmission and playing an integral role in controlling anxiety-like behaviors. While the effect of ethanol on the amygdala and anxiety-like behaviors is well-established, sex differences in the effects of ethanol on BLA neurophysiology and the effect of ethanol on traumatic stress-induced changes to BLA activity are currently unknown. Understanding the sex-related factors that contribute to BLA neuron membrane properties in stressed animals may point to potential neural mechanisms associated with gender differences in resilience or susceptibility to stress and improve individualized treatment. Ethanol-mediated inhibition is stronger in BLA neurons from males than females and ethanol-mediated inhibition of hyperpolarization-activated, cyclic nucleotide gated current (Ih) is stronger in males, owing in part to the low amplitude of Ih in females in the absence of ethanol. In response to SPS, action potential firing in the BLA did not change between males and females. However, ethanol significantly decreased action potential firing in BLA neurons exposed to SPS in females only, suggesting that the inhibitory effect of alcohol is greater in females than in males exposed to stress. Ethanol decreased Ih amplitude only in BLA neurons from males exposed to SPS, in part because Ih amplitude is larger in BLA neurons from males than it is in females. Since ethanol reduced BLA excitability only in males, these data suggest that ethanol may be more anxiolytic in males than in females. This difference may contribute to the sex differences in comorbid PTSD and alcohol abuse.