Neuroscience Letters, 104 (1989) 281~85 281 Elsevier Scientific Publishers Ireland Ltd. NSL 06342 Evidence for a widespread dopaminergic innervation of the human cerebral neocortex Jacques De Keyser l, Guy Ebinger I and Georges Vauquelin 2 1Department of Neurology, Academisch Ziekenhuis, Vrije Universiteit Brussel, Brussels (Belgium) and 2Department of Protein Chemistry, Vrije Universiteit Brussel, St. Genesius Rode (Belgium) (Received 28 February 1989; Revised version received 29 May 1989; Accepted 29 May 1989) Key words." Dopamine receptor; Dj receptor; Human brain; Cortex; Dopaminergic innervation; SCH 23390 The recent finding that D~ dopamine receptors are present in all neocortical areas of the human brain, does not fit in with the generally held view that the mesocortical dopaminergic pathway is restricted to prefrontal areas. We investigated the brains of 3 patients who died with a unilateral infarction in the ven- tral midbrain, including the substantia nigra and ventral tegmental area. Compared to the intact side, the D~ receptors in frontal, temporal, parietal and occipital cortices and caudate nucleus at the lesioned side were increased by 27-37%, which is consistent with an up-regulation in response to a depletion of dopa- mine. These data provide evidence for a more widespread dopaminergic innervation of the human neocor- tex. The assumption that the human prefrontal cortex receives a mesencephalic dopa- minergic projection stems from histofluorescence studies carried out in rats in the ear- ly 70s [9, 14]. Although no convincing evidence for a similar pathway was given in man, there have been speculations on its possible contribution to the symptomatol- ogy of schizophrenia [9], Parkinson's disease [10] and Tourette's syndrome [1]. No differences exist in the concentrations of dopamine and its metabolites between frontal cortex and the other neocortical areas; the concentrations being very low in all compared to the neostriatum [7]. Dopamine is also a precursor of noradrenaline and adrenaline. Therefore, the classical histochemical methods for demonstrating dopaminergic nerve fibers are not suitable for post-mortem human brain, because they require ante-mortem lesions in order to eliminate noradrenergic and adrenergic neurons. Mapping out the dopamine receptors may improve our insights in the orga- nisation of the dopaminergic neuronal system in the human brain. There are two major classes of dopamine receptors, termed D1 and D2 [11]. D2 receptors have not been detected in human neocortex, with the exception of doubtful Correspondence: J. De Keyser, Department of Neurology, Akademisch Ziekenhuis V.U.B., Laarbeeklaan 101, B-1090 Brussels, Belgium. 0304-3940/89/$ 03.50 © 1989 Elsevier Scientific Publishers Ireland Ltd.