Influence of neuronal activity levels on the cytotoxic effects of guanethidine.

Reduction of activity levels in the noradrenergic innervation of the iris of the rat by decentralization of the superior cervical ganglion resulted in a marked increase in sensitivity of these fibers to damage by chronic guanethidine treatment (15 mg/kg/day) as shown by fluorescence histochemistry. Guanethidine also had an increased cytotoxic effect on the decentralized nerve cell bodies. These results suggest that the relative inactivity of male "short" noradrenergic neurons may contribute to their sensitivity to damage by guanethidine. The nature of the damage produced in other tissues by this dose of guanethidine indicates that levels of neuronal activity are not the only factor determining sensitivity to the cytotoxic effects of this drug.