Effects of hypoxic-ischemic brain damage on dopaminergic markers in the neonatal rat: a regional autoradiographic analysis

Dopamine has been implicated as an endogenous substance that may mediate neuronal death after hypoxic-ischemic in-sult. Using semiquantitative autoradiography, we studied the effect of perinatal hypoxic-ischemic injury on dopamine binding sites in rat brain. Experimental injury resulted in a substantial decrease in dopamine type-1 (D1) and forskolin (adenylate cyclase) binding sites. In contrast, markers for dopamine type-2 (D2) sites and for dopamine uptake were un-affected in lesioned animals. Changes within dopaminergic pathways were variable, with reduction in binding being en-countered mainly in components of the extrapyramidal motor system: caudate-putamen,-61%; globus pallidus,-64%; entopeduncular nucleus,-60%; and substantia nigra,-69%. Furthermore, the topography of D1 receptor loss within the caudate-putamen was not uniform, with the greatest decrement in dorsolateral regions. Reduced D1 versus D2 receptor activation may underlie extrapyramidal movement disorders that appear as a consequence of perinatal hypoxic-ischemic insult. (J Child Neurol 1992;7:199-207). rain injury from cerebral hypoxia and isch-emia is clearly responsible for a portion of the static encephalopathies of childhood.l-5 Neuro-logic expressions of these injuries include seizure disorders, mental retardation, and cerebral palsy