the nucleus accumbens (21, 46, 47). Such studies, based on locomotor sensitization as the behavioral indicator of addiction sensitivity, have led to the speculation that overexpression of Homer reduces addiction vulnerability (21, 46, 47). However, no animal investigation has evaluated Homer regulation specifically in the amygdala, thus brain region-specific disturbances in the long Homer isoforms might underlie different components of the addiction phenotype. This is particularly relevant since it has been recently documented, for example, that Homer 1b/c is differentially altered in the nucleus accumbens (decreased) and prefrontal cortex (increased) after early drug withdrawal in animals that self-administered cocaine (48). Moreover, the prefrontal cortical increase of Homer 1b/c was only evident in animals that experienced daily, extended access to cocaine self-administration (48), an animal model mimicking loss of control over drug intake, compared to animals with only short access to the drug. Such findings implicate an important contribution of compulsive drug use to the cortical Homer 1b/c alterations. It remains to be studied whether allocortical amygdala Homer 1 b/c alterations are more comparable to those evident in the prefrontal cortex in contrast to that seen in the nucleus accumbens. The current results obtained by the direct investigation of human abusers
