Self-injurious behavior and dopaminergic neuron system in neonatal 6-hydroxydopamine-lesioned rat: 1. Dopaminergic neurons and receptors.

Dopaminergic neuronal circuits underlying self-injurious behavior (SIB) were investigated in neonatal 6-hydroxydopamine (6-OHDA)-induced dopamine-depleted rats. The extent of damaged dopamine neuronal areas was investigated by quantitative analysis of tyrosine hydroxylase (TH) immunocytochemistry and the biochemical quantification of dopamine levels in three groups; neonatal 6-OHDA-treated rats showing SIB (the SIB(+) group), neonatal 6-OHDA-treated rats not showing SIB (SIB(-) group) and neonatal saline-treated controls (control group). In the SIB(+) group, both dorsal and ventral mesostriatal dopaminergic neuron systems were severely destroyed, but the mesocortical dopaminergic neuron system and intrahypothalamic dopaminergic neuron system remained intact. In SIB(-) group, the dorsal mesostriatal dopaminergic neuron system was severely destroyed, but the ventral mesostriatal dopaminergic neuron system was only partially impaired. The effect of neonatal 6-OHDA treatment on dopaminergic receptors was analyzed by quantitative in vitro receptor autoradiography using [3H]SCH-23390 for the D1 site and [3H]YM-09151-2 for the D2 site. Although D1 and D2 binding was not altered in the dorsal and ventral striatum, cerebral cortex and hypothalamus, the D1 binding in the substantia nigra pars reticulata was increased in the SIB(+) group compared with the SIB(-) or control groups. The D1 binding assay using the membrane preparation of the nigral homogenates, revealed that the KD did not change, but the Bmax in the SIB(+) group was higher than that in the SIB(-) or control groups (P < .05). These results suggest that the region-specific change of dopaminergic neurons and receptors underlies the manifestation of SIB.