Glutamatergic neurotransmission is the primary regulator of activity-dependent synaptic modifications that underlie experience-dependent brain plasticity (Chandler, 2003). As will be discussed in the next section, both acute and chronic alcohol exposure significantly impact glutamatergic neurotransmission in the PFC. In addition, results from several studies suggest that plastic processes of associative learning overlap and interact with those that underlie the development of addictive behaviors (Berke and Hyman, 2000). Addiction is clearly a complex disease that involves motivational and higher-order cognitive processes that initiate and control goal-directed behaviors, and accumulating evidence implicates altered glutamatergic neurotransmission mediated by projections to and from the prefrontal cortex in the neuroplasticity of addiction (Jentsch and Taylor, 1999; Kalivas, 2009). The PFC is highly integrated into the addiction neurocircuitry. Addictive behaviors, such as those associated with alcohol abuse and alcoholism, include loss of control over consumption and 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
