Evidence on the retrograde neurotoxicity of doxorubicin.

Doxorubicin, a fluorescent retrograde neurotoxin, killed neurons in the ventral tegmentum and thalamus that were afferent to the injection site in the caudate-putamen. The neurotoxic effects in the ventral tegmentum and thalamus were prevented by a large coronal knife cut caudal to the injection site in the striatum, suggesting that retrograde transport of doxorubicin is necessary for the death of afferent neurons. In the striatum the neurotoxic effects of doxorubicin 14 days post-injection were quantitatively much greater on afferent neurons (as assessed by a 72% drop in dopamine levels) than on local striatal perikarya (as evidenced by the small 22% drop in the activity of glutamic acid decarboxylase). Doxorubicin may be a useful tool for selectively destroying, by way of retrograde transport, neurons that are afferent to a site in the brain.