Alcoholism (
alcohol dependence) is characterized by a compulsion to seek and ingest alcohol (
ethanol), loss of control over intake, and the emergence of a negative emotional state during withdrawal. Animal models are critical in promoting our knowledge of the neurobiological mechanisms underlying
alcohol dependence. Here, we review the studies involving operant alcohol
self-administration in rat models of
alcohol dependence and withdrawal with the focus on the alcohol vapor model. In 1996, the first articles were published reporting that rats made dependent on alcohol by exposure to alcohol vapors displayed increased operant alcohol
self-administration during acute withdrawal compared with nondependent rats (i.e., not exposed to alcohol vapors). Since then, it has been repeatedly demonstrated that this model reliably produces physical and motivational symptoms of
alcohol dependence. The functional roles of various systems implicated in stress and reward, including
opioids,
dopamine,
corticotropin-releasing factor (CRF),
glucocorticoids,
neuropeptide Y (NPY), γ-
aminobutyric acid (
GABA),
norepinephrine, and
cannabinoids, have been investigated in the context of
alcohol dependence. The combination of models of alcohol withdrawal and dependence with operant
self-administration constitutes an excellent tool to investigate the neurobiology of
alcoholism. In fact, this work has helped lay the groundwork for several ongoing clinical trials for
alcohol dependence. Advantages and limitations of this model are discussed, with an emphasis on what future directions of great importance could be.