Activation by alcohol of prefrontal layer 5 pyramidal neurons depends on ascending dopaminergic input

Understanding the initial actions of alcohol on brain circuits can reveal mechanisms that drive the transition from controlled drinking to addiction. Although alcohol increases dopamine release in midbrain reward regions such as the ventral tegmental area (VTA), it remains unclear how executive cortical regions such as the prefrontal cortex (PFC) are modulated by dopamine during acute alcohol exposure. Here, using mice, we show that alcohol activates PFC pyramidal neurons and that this activation requires dopaminergic signaling from the VTA. This dopaminergic modulation of PFC activity provides insight into early circuit-level vulnerabilities and suggests potential therapeutic targets relevant to alcohol addiction.