Relation between rotation in the 6-OHDA, lesioned rat and dopamine loss in striatal and substantia nigra subregions

The relation between the rotation response to drug-induced activation of the dopamine (DA) receptor in the rat unilaterally lesioned with 6-hydroxydopamine (6-OHDA) in the substantia nigra (SN) and the loss of DA in subregions of the SN and caudate-putamen (C/PUT) is not clear. Here this relation was examined in 23 rats classified as rotators to amphetamine (5 mg/kg). After their response was characterized in terms of ipsilateral rotation, contralateral rotation, and oral stereotypy in one place, they were divided into high, medium, low, and very low rotators. The loss of DA in each group was visualized on brain sections immunoreacted to tyrosine hydroxylase (TH). The density of the TH label on the side of the lesion was compared to that on the intact side. In the ventral midbrain, the density was determined in the SN subdivided into far lateral, lateral, central, and medial subregions and also in the ventral tegmental area (VTA). In the forebrain, it was determined in the C/PUT subdivided into lateral, central, and medial subregions and also in the nucleus accumbens (ACC). These measurements led to three principal findings. The first was a positive overall correlation between rotation and loss of TH label. The second was a correlation between rotation and penetration of the loss from the lateral subregions into more medial areas. The third was a larger loss in SN and VTA (midbrain) than in C/PUT and ACC (forebrain). These findings show that rotation depended not only on the overall loss of DA but also on its distribution across subregions. The loss in the lateral subregion, always the largest regardless of the rate of rotation, may have been the first step in inducing the motor abnormality, and the loss in the central and medial subregions may have served to enhance the abnormality due to the loss in the lateral subregion.