Reduction of cortical dopamine, noradrenaline, serotonin and their metabolites in Parkinson's disease

Abstract

Dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, noradrenaline, serotonin and 5-hydroxyindoleceatic acid concentrations were measured in several cortical areas, hippocampus and, for comparison, in the caudate nucleus, from control subjects and parkinsonian patients. Substantia amounts of these compounds were detected in hippocampus, and entorhinal, cingulate and frontal cerebral cortices of control subjects. In patients who had discontinued l-DOPA at least 4 days before death (group I), the levels of dopamine and its metabolites were reduced in these cortical areas, although to a lesser extent than in the caudate nucleus. In patients on continuous l-DOPA treatment (i.e. having received the last dose of l-DOPA 0–24 h before death, group II), cortical dopamine levels were less reduced than in group I patients and dopamine metabolite levels were similar to those of controls. The ratio of the concentrations of homovanillic acid to dopamine was increased in the caudate nucleus and entorhinal cortex but not in the other cortical areas of group I parkinsonian patients. Cortical noradrenaline concentrations were also diminished, the decrement being similar in groups I and II. A reduction of serotonin and its metabolite in the caudate nucleus and hippocampus and a diminution of serotonin levels in the frontal cortex were observed in group I patients. In these patients, the 5-hydroxyindoleacetic acid to serotonin ratio was increased in the caudate nucleus and frontal cortex but not in the other cortical areas. The results are discussed in relation to the pathophysiology of the psychiatric and cognitive disturbances observed in some parkinsonian patients.