Acute alcohol in prefrontal cortex is characterized by enhanced inhibition that transitions to excitation.

Acute alcohol can have profound effects on the brain and behavior. Dorsal medial prefrontal cortex (dmPFC) function is especially sensitive to disruption from acute alcohol exposure. The acute, broadly inhibitory pharmacodynamics of alcohol in dmPFC have been well characterized in in vitro and ex vivo preparations, but seemingly contradict the stimulatory behavioral effects of alcohol at low-to-moderate doses. To determine the effects of acute alcohol on dmPFC activity, this study combined multiple routes of alcohol exposure across multiple rodent species and preparations and utilized modeling techniques to make direct predictions about brain ethanol concentrations. These findings revealed that the acute effects of alcohol on dmPFC are actually biphasic in nature, such that broad reductions in activity are immediately followed by broad increases in neural activity. Notably, these increases in neural activity were only observed in in vivo preparations, suggesting that network engagement and exposure route may be critical.