Effects of reserpine on fast, intermediate and slow axonal transport of proteins in rat locus coeruleus neurons

The effects of a single injection of reserpine (5 mg/kg, i.p.) on protein turnover and axonal transport (AT) in locus coeruleus (LC) noradrenergic neurons was investigated in the rat. Reserpine pretreatment, at intervals of 1–21 days prior to [³H]-fucose or leucine injection into the LC, resulted in marked alterations in the turnover of [³H]glycoproteins and proteins in the LC and hypothalamus which were present for up to 14 days and varied according to the time after reserpine pretreatment. Reserpine produced an intermittent blockade, of variable degree, in rapidly and intermediately transported proteins for up to 2 weeks following injection. Slow AT was uniformly decreased over the first 10 post-treatment days to 2–42% of controls. Blockade and not a change in the rate or time of onset of transport appeared to be responsible for the observed changes. The suggested mechanism for these alterations is a re-ordering of metabolic priorities in the synthesis and transport of proteins in these noradrenergic cells secondary to a reserpine-induced depletion of norepinephrine in the nerve terminals.