State-dependent alteration of dopamine and glutamate transmission in the prefrontal cortex by psychostimulants

In spite of accumulating evidence for dopaminergic contribution to cognitive functions, the mechanism of how the cortical dopamine (DA) level is controlled is still obscure. To investigate the mechanisms of intracortical DA level control, this article investigates the dynamics of the prefronto-mesoprefrontal system under the influence of the DA releaser or the psychostimulant. The fundamental assumption of this model is closed-loop circuitry between the prefrontal cortex (PFC) and the midbrain DA nuclei. This study suggests that the system forms a regulator with peculiar characteristics. These characteristics would be responsible for state-dependent responses to psychostimulants and may have relevance to negative symptoms and cognitive deficits in schizophrenia.