relapse to drinking. The PFC normally exerts “top-down” (e.g., information derived from prior experience) inhibitory control over internal and external sensory-driven compulsive behaviors. Increasing evidence suggests that continued drug exposure leads to attenuation of the ability of the PFC to monitor and inhibit these behaviors, with eventual loss of inhibitory control over drinking. Volkow and colleagues have conceptualized this loss of inhibitory control by the PFC as a syndrome of “impaired response inhibition and salience attribution” (Goldstein and Volkow, 2002; Volkow et al., 2003). This syndrome is envisioned to encompass an integrated cluster of addictive behaviors that depend upon interaction with the PFC. An important feature of the PFC is that it is functionally and structurally adaptable, and a major component of cortical cognitive processing is that it is highly influenced by “knowledge” of past experiences. Thus, reward information such as that provided by the VTA dopaminergic system has a pervasive and lasting influence on the activity of the PFC.
