Dopaminergic growth patterns induced by striatal and cortical grafts show differences in sensitivity to increased striatal trophic activity induced by haloperidol

During development, dopaminergic neurons innervate the developing striatal target, forming two different growth patterns: a patchy growth and a diffuse growth. Chronic treatment with the dopamine antagonist haloperidol increase the neurotrophic activity in striatum, but it is not known how this trophic activity influences different patterns of dopaminergic growth. In this paper we have studied dopaminergic growth patterns by evaluating tyrosine hydroxylase (TH)-positive growth from mature midbrain dopaminergic neurons innervating grafted fetal lateral ganglionic eminence (LGE) or fetal cortical tissue implanted into the dorsal striatum. Host dopaminergic neurons innervated LGE grafts with a patchy growth pattern, leaving large portions of the striatal graft noninnervated, and cortical grafts with diffuse, nonpatchy growth, evenly distributed over the total volume of the graft. Both types of growth patterns were enhanced over time, albeit the most pronounced change was found in the nonpatchy pattern in the cortical grafts. When fetal LGE or cortical tissues were transplanted into the dorsal striatum of chronically haloperidol-treated animals, the nonpatchy growth into fetal cortical grafts was enhanced while the patchy growth into fetal striatal tissue was not. Taken together, the results suggest that both the patchy and diffuse growth patterns may be induced from adult midbrain dopaminergic neurons depending on the target of innervation, and that increased striatal trophic activity due to blockade of the dopaminergic input stimulates growth from a subpopulation of dopaminergic neurons that produce the nonpatchy growth.