The Relevance of the Dopamine-D1 Receptor in the Cognitive Symptoms of Schizophrenia

An understanding of the role of the prefrontal cortex in normal cognitive processes has advanced our comprehension of the pathophysiology underlying the cognitive deficits in schizophrenia. Studies of single-neuron activity in monkeys during performance of delayed-response tasks have confirmed the involvement of the prefrontal cortex in working memory. The “memory fields” of prefrontal neurons are analogous to the receptive fields of visual neurons and the cellular expression of a working memory process that allows mnemonic information to guide behavior. D1-dopamine antagonists produce a dose-dependent effect (U-shaped) on the firing rate of cells with memory fields during delayed-response tasks. Disordered cognitive processes in schizophrenia can be attributed to impairment of function in the prefrontal cortex, as evidenced by hypometabolic activity in the prefrontal cortex and selective impairment in working memory tasks. Advances in our understanding of the role of D1 receptors in the cognitive deficits observed in schizophrenia should provide us with a rational basis for developing alternative antipsychotic treatments and may provide insight into the cellular basis of the disorder.