Alcoholism is a devastating condition that represents a progression from initial alcohol use to dependence. Although most individuals are capable of consuming alcohol in a limited fashion, the development of alcohol dependence in a subset of individuals is often associated with negative emotional states (including anxiety and depression). Since the alleviation of this negative motivational state via excessive alcohol consumption often becomes a central goal of alcoholics, the transition from initial use to dependence is postulated to be associated with a transition from positive to negative reinforcement mechanisms. Vasopressin is a neuropeptide known to potentiate the effects of CRF on the HPA axis, and emerging evidence also suggests a role for centrally located vasopressin acting on V_1b receptors in the regulation of stress‐ and anxiety‐like behaviors in rodents. The present study determined state‐dependent alterations in vasopressin/V_1bR signaling in an animal model of ethanol dependence. The V_1bR antagonist SSR149415 dose‐dependently reduced excessive levels of ethanol self‐administration observed in dependent animals without affecting the limited levels of ethanol drinking in non‐dependent animals. Ethanol self‐administration reduced V_1b receptor levels in the basolateral amygdala of non‐dependent animals, a neuroadaptation that could theoretically facilitate the positive reinforcing effects of alcohol. In contrast, V_1bR levels were seemingly restored in ethanol‐dependent rats, a switch that may in part underlie a transition from positive to negative reinforcement mechanisms with dependence. Together, our data suggest a key role for vasopressin/V_1bR signaling in the transition to ethanol dependence.