Effects of Hypoxic-Ischemic Brain Damage on Dopaminergic Markers in the Neonatal Rat: A Regional Autoradiographic Analysis

Abstract

Dopamine has been implicated as an endogenous substance that may mediate neuronal death after hypoxic-ischemic insult. 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 unaffected in lesioned animals. Changes within dopaminergic pathways were variable, with reduction in binding being encountered 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).

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