Effects of reserpine on activities and amounts of tyrosine hydroxylase and dopamine-beta-hydroxylase in catecholamine neuronal systems in rat brain.

Reserpine (10 mg/kp i.p.) increased the activities of the enzymes tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase, but not dopa decarboxylase, 2- to 3-fold in the nucleus locus ceruleus of rat brain. The TH response was dose-dependent, reached a maximum by 48 hours and recovered by 3 weeks. The increased activities of TH and dopamine-beta-hydroylase were shown by immunotitration with specific antibodies to each enzyme to be due entirely to increased accumulation of specific enzyme protein. At a time when the reserpine-elicited accumulation of TH was increased 300% in the locus ceruleus, activity of the enzyme only increased 20% in hypothalamus and not at all in substantia nigra or caudate nucleus. Reserpine increased the accumulation of TH, primarily in the cell bodies and to a far less degree in the terminals of neurons of locus ceruleus but not in dopaminergic neurons of the nigrostriatal system. The time course of enzyme accumulation parallels that of depletion of monoamines in brain.