Oxytocin Modulation of Nonsocial Anxiety-Related Behavior and Glutamate Plasticity following Adolescent Intermittent Ethanol Exposure

Initiation of alcohol use typically begins during adolescence in humans, with males reporting higher binge-drinking levels. In rodent models, the long-term developmental consequences of adolescent alcohol (ethanol) exposure include retention of some adolescent-like phenotypes such as anxiety-related responding into adulthood. Recently, it has been shown that neuromodulation via the oxytocin system selectively alleviates social anxiety in adult males following adolescent intermittent ethanol (AIE) exposure. In the current study, we investigated whether an oxytocin agonist would also result in anxiolytic effects in a nonsocial anxiety-related task, novelty induced hypophagia. Both adult males and females exhibited enhanced anxiogenic-like responding during task training following AIE exposure. The nonpeptide oxytocin agonist WAY-267464 increased anxiolytic responding in males, but increased anxiogenic responding in females, independent of adolescent exposure. We further assessed glutamate receptor expression to provide further insight into oxytocin’s mode of action in males. Multiple effects were noted for NMDA and AMPA receptor plasticity within the lateral septum and amygdala, but not the ventral hippocampus. Overall, these findings further validate oxytocin’s anxiolytic mechanism of action in males and further suggest responses may involve regulation of glutamate receptor subtypes