Schizophrenic deficits: Neuroleptics and the prefrontal cortex-a reply

In their commentary, Jobe et al. point out that the primary action of neuroleptics is to decrease dopamine activity. They note that this fact, along with the therapeutic effect of these medications in schizophrenia, would seem to be inconsistent with the hypothesis that schizophrenia is associated with a decrease of dopamine activity in the prefrontal cortex. In this reply, we clarify our position on the relationship between disturbances of dopamine activity in schizophrenia and the action of neuroleptic medications. In particular, we review a more detailed discussion of this issue that we provided in an earlier report, in which we proposed many of the same ideas described by Jobe et al., that may reconcile the pharmacological and behavioral effects of neuroleptics with our theory concerning disturbances of dopamine in schizophrenia. Chief among these is the possibility that neuroleptics may help correct an imbalance in dopaminergic activity between cortical and subcortical systems.