CeA-projecting VTA neurons contribute to alcohol withdrawal-induced anxiety-like behavior in male and female rats.

Alcohol use disorder often causes patients to experience negative affect during withdrawal, and anxiety is positively correlated with relapse during abstinence. The neural adaptations that occur during the transition to dependence are not entirely understood, but they may include interactions between mesolimbic reward circuits and brain stress circuits. Previously, we demonstrated that chronic alcohol exposure leads to activation of ventral tegmental area (VTA) neurons projecting to the central amygdala (CeA) during acute withdrawal, raising the possibility that these cells may underlie some behavioral changes observed during alcohol withdrawal. Here, we investigated the role of VTA-CeA circuitry in anxiety-like behavior during acute alcohol withdrawal in rats. Using a dual virus approach to transfect CeA-projecting VTA neurons with excitatory or inhibitory DREADDs, we demonstrate that VTA-CeA circuit activation increases anxiety-like behavior in otherwise experimentally naïve adult male and female Wistar rats, and that VTA-CeA circuit inhibition rescues increased anxiety-like behavior during acute withdrawal from chronic alcohol exposure. Collectively, the results of these experiments suggest that VTA-CeA circuitry may contribute to anxiety-like behavior and may serve as a target for alleviating alcohol withdrawal-induced anxiety.