Degeneration and Regrowth of Adrenergic Nerve Fibers in the Rat Peripheral Tissues after 6-Hydroxydopamine

Abstract

Histofluorescent and biochemical changes in the adrenergic nervous system were followed up in rat tissues after one single intravenous injection of a high dose of 100 mg/kg of 6-hydroxydopamine (6-OH-DA). This treatment results in the rapid disappearance of terminal and preterminal fibers in the iris, atria, and small arteries of rats, whereas endogenous noradrenaline pools of the heart are 95% depleted. The capacity of the adrenergic nerve to take up and accumulate tritiated noradrenaline is reduced proportionally to the reduction in endogenous noradrenaline levels. These changes are compatible with the concept of a complete sympathectomy induced by the specific toxic action of 6-OH-DA on the adrenergic fibers. This sympathectomy is not permanent, however, and numerous bundles of preterminal fibers start to grow in the iris and atria within 4 to 5 days following injection. Progressively, in the following weeks, these fibers distribute over the whole organ and give birth to terminal fibers which form a new adrenergic plexus in these tissues. A completely normal innervation is restored 2 to 3 months after administration of 6-OH-DA. The endogenous noradrenaline levels rise progressively in parallel to the development of the new plexus of fibers. Since a complete regeneration of the adrenergic innervation can be demonstrated in the weeks following injection of 6-OH-DA, it appears that this compound can selectively destroy the adrenergic terminal and preterminal fibers without causing a degeneration of the adrenergic ganglion cells.