The persistent effects of predator odor stressor enhance interoceptive sensitivity to alcohol through GABA receptor adaptations in the prelimbic cortex in male, but not female rats.

Background: Traumatic stress is associated with high rates of problematic alcohol use, but how the persistent effects of trauma impact sensitivity to alcohol remain unknown. This study examined the persistent effects of traumatic stress exposure on sensitivity to alcohol and underlying neurobiological mechanisms in rats.

Methods: Male (N=98) and female (N=98) Long-Evans rats were exposed to the predator odor TMT, and two weeks later, molecular, neuronal, and behavioral sensitivity to alcohol were assessed.

Novel RXFP3 negative allosteric modulator RLX-33 reduces alcohol self-administration in rats.

There is much interest in identifying novel pharmacotherapeutic targets that improve clinical outcomes for the treatment of alcohol use disorder (AUD). One promising target for therapeutic intervention is the relaxin family peptide 3 (RXFP3) receptor, a cognate receptor for neuropeptide relaxin-3, which has previously been implicated in regulating alcohol drinking behavior. Recently, we developed the first small-molecule RXFP3-selective negative allosteric modulator (NAM) RLX-33.