The role of accumbal hypoactivity in cocaine addiction.

Cocaine-induced hypoactivity of the nucleus accumbens (NAC) is hypothesized to contribute to cocaine addiction. There are two important questions related to this hypothesis. First, cocaine addiction is characterized by an increase in drug-directed behavior and a simultaneous weakening of other motivated behaviors. However, the NAC contributes to both drug- and nondrug-directed behavior. Moreover, the nature of the contributions is similar and associated predominantly with excitatory phasic firing patterns. Given these observations, it is not clear how hypoactivity of NAC neurons might contribute to the behaviors that characterize cocaine addiction. Second, various types of investigations have documented neurochemical and molecular adaptations that could underlie NAC hypoactivity. However, there is also evidence of other adaptations in the NAC and in NAC afferents, which are expected to have an excitatory influence on NAC neural activity. In the present review, we will briefly overview these issues. We will also describe a hypothesis and related empirical evidence that may contribute to answering these questions. Further investigation of the issues and the hypothesis may contribute to a better understanding of the neuroadaptations that contribute to cocaine addiction.