Baicalein blocks ethanol effects on dopamine transmission in the mesolimbic system and ethanol self-administration

The dopamine (DA) projection from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) is implicated in ethanol (EtOH) reward. While EtOH increases VTA DA neuron firing and basal DA release, it paradoxically reduces evoked DA release in the NAc. This study evaluated whether baicalein, a flavonoid antioxidant from Scutellaria baicalensis, modulates EtOH-induced inhibition of evoked DA release and EtOH reward. Using fast-scan cyclic voltammetry (FSCV), baicalein (10-100 μM) alone did not affect evoked DA release but significantly attenuated EtOH-induced inhibition (80 mM) in mouse NAc ex vivo. Similarly, in vivo FSCV in rats showed that baicalein (1-40 mg/kg, i.p.) did not alter evoked DA release but reduced EtOH-induced inhibition (2.5 g/kg). In a sucrose-fading EtOH self-administration paradigm, baicalein decreased EtOH intake without impairing task performance; however, sucrose self-administration was also reduced. These findings indicate that baicalein diminishes EtOH reward, likely through modulation of evoked DA signaling in the NAc, but its effects are not specific to EtOH reinforcement. Given its minimal independent effects and low toxicity, baicalein may have therapeutic potential for alcohol use disorder.