In the basal ganglia, centrally active suicide transport agents produce apparently selective lesions of the striatopallidal and striatonigral pathways based on receptor binding and
neuropeptide mRNA studies. In the present study we sought to determine the selectivity of suicide transport lesions for specific subsets of striatal neurons. Using immunohistochemical methods, the neostriata of adult rats were examined 10 days after an injection of
volkensin into the substantia nigra or an injection of
OX7-saporin into the globus pallidus.
Ricin, a suicide transport agent active in the peripheral but not the central nervous system, was injected into each target as a control. Adjacent sections were processed for (1) Nissl
stain to assess neuronal density, both overall and for large interneurons, (2)
NADPH-diaphorase (
NADPH-d) histochemistry, to mark medium-sized aspiny interneurons, (3)
enkephalin immunocytochemistry, to label striatopallidal neurons, or (4)
substance P immunocytochemistry, to label striatonigral neurons.
Ricin injections produced no change in the densities of these subsets of striatal cells. In animals receiving
volkensin or
OX7-saporin injections, analyses of Nissl material revealed that the striata ipsilateral to the toxin
injections appeared normal and did not exhibit shrinkage or
gliosis; however, a quantitation analysis revealed a moderate decrease in cell density (12-16% loss, P < 0.01). The densities of both large and
NADPH-d-containing striatal interneurons were unchanged after lesions in either target. Following nigral
injections with
volkensin, the density of striatal
substance P-labeled cells decreased (26% loss, P < 0.01), while the density of
enkephalin-labeled cells did not decrease significantly (11% decrease, P > 0.1). After pallidal
injections with
OX7-saporin, the density of striatal
enkephalin-labeled cells decreased (20% loss, P < 0.01), while that of
substance P-labeled cells remained unchanged. These data show that nigral
volkensin and pallidal
OX7-saporin injections differentially lesion striatonigral and striatopallidal projection neurons and spare striatal interneurons. This study provides further evidence for the selectivity, specificity, and utility of suicide transport agents to study brain structure and function.