Experimentally-induced neuron loss in the locus coeruleus of adult rats

Systemic administration of the noradrenergic neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) to adult rats causes widespread degeneration of locus coeruleus (LC) axon terminals. The present study was conducted to determine the effects of DSP-4-induced LC axon lesions on LC cell bodies. Six months after DSP-4 treatment, quantitative analysis of Nissl-stained sections revealed a profound loss of LC perikarya, ranging from 20 to 73% of control. The remaining LC neurons appeared shrunken, but stained strongly with dopamine beta-hydroxylase immunohistochemistry. These findings support the conclusion that DSP-4-induced LC axon lesions cause retrograde degeneration of LC neurons. DSP-4 may serve as a useful tool in studies of the mechanisms of LC neuron degeneration.