Post-weaning social isolation of rats produces an array of behavioral and neurochemical changes indicative of altered dopamine function. It has therefore been suggested that post-weaning social isolation mimics some aspects of schizophrenia. Here we replicate and extent these findings to include an investigation of prefrontal cortical dopamine dynamics using in vivo microdialysis. Social isolation for 12 weeks after weaning caused increased locomotor activity in response to novelty and amphetamine challenge. In vivo microdialysis experiments revealed that while social isolation did not change basal dopamine levels in the nucleus accumbens, it did cause a significant reduction of basal dopamine release in the prefrontal cortex. In addition, social isolation lead to a significantly larger dopamine response to an amphetamine challenge, in both the nucleus accumbens and the prefrontal cortex compared to group housed controls. Taken together, these results indicate that post-weaning social isolation alters dopaminergic function with changes resembling subcortical hyperdopaminergia and prefrontal hypodopaminergia similar to what has been observed in schizophrenic patients.