DEGENERATION OF LOCUS-COERULEUS AXONS IN STRESS-INDUCED DEPRESSION MODEL

Antidepressants such as desipramine induce axonal regeneration of brai n noradrenergic neurons. This novel action of antidepressants suggests the involvement of degeneration or retraction of brain noradrenergic axons in the pathophysiology of clinical depression. The present study was designed to further confirm this view in an animal model of stres s-induced depression. The depression model was produced by exposing ra ts to prolonged forced walking stress. To see if axonal degeneration o f noradrenergic neurons occurred in the depression model, the density of noradrenergic axons in the cerebral cortex was assessed by three di fferent methods, antidromic stimulation technique, retrograde tracing with horseradish peroxidase, and immunohistochemical staining with dop amine-P-hydroxylase antiserum. These methods all assured of degenerati ve changes of noradrenergic axon terminals in the depression model. Fu rthermore, it was found that repeated treatments of the depression-mod el rats with imipramine could cause regeneration of cortical noradrene rgic axons. These findings support the view that degeneration or retra ction of noradrenergic axons is involved in the pathophysiology of dep ression.