This chapter considers recent data from animal studies that may suggest an integration of the dopaminergic dysregulation affected by neuroleptic drugs and the cortical defects that may be at the core of the illness. The reviewed data raise the possibility that abnormalities in the dopamine (DA) system may be secondary effects of cortical dysfunction rather than primary causes of the disease. The chapter shows that neurodevelopmental events may play an important role in “bringing up” and/or exaggerating the dopaminergic effects of subtle cortical dysfunction induced neonatally. It analyses the role of stress on the DA mesolimbic system in animals with dysfunctional cortices, since stress has been implicated on numerous occasions in the onset and relapse of schizophrenia. The neurotransmitter system most strongly implicated in schizophrenia is the mesolimbic DA system. There are several mechanisms by which limbic-cortical regions may modulate mesolimbic DA transmission.