Mechanisms for the Interaction of Dopamine andNorepinephrine in the Prefrontal Cortex: Implications for the Treatment of Cognitive Symptoms ofSchizophrenia
Neuroscience Graduate Program, Vanderbilt University School of Medicine, U1205 Medical Center North, Nashville, TN 37232, USA.
Abstract | Reductions in prefrontalcortical dopamine (DA) levels have been associated with the cognitive symptomsof schizophrenia. When removal of the dopamine innervation to the prefrontalcortex (PFC) was tested in animal models, researchers reported a loss ofdendritic spines. Anatomical arrangements in the PFC suggest that dopamine mayplay a role in the regulation of dendritic architecture. Atypicalantipsychotics, but not typical antipsychotics, reverse the loss of dendriticspines seen upon DA denervation. Atypical antipsychotic drugs have also beenreported to reduce cognitive symptoms of schizophrenia. Taken together withtheir ability to reverse spine loss, these data suggest that spine loss may bea pathological correlate to cognitive deficits associated with the prefrontalcortex. The mechanism by which these drugs act to restore DA tone in the PFCremains unclear. Recent data has suggested that norepinephrine (NE) terminalsare capable of releasing the NE “precursor” DA. Atypical antipsychotic drugshave a wide target profile, including antagonism of NE autoreceptors. Thesedata suggest that interactions between the DA and NE systems may play a role intreatment for schizophrenia. Although DA and NE have been implicated indisorders involving the prefrontal cortex such as schizophrenia, affectivedisorders, and attention-deficit hyperactivity disorder (ADHD), the mechanismfor interactions between DA and NE has not been widely investigated.Understanding how these systems interact should have a major impact ontherapeutic possibilities for disorders arising from disruption of PFC function.