Long-term stress degenerates, but imipramine regenerates, noradrenergic axons in the rat cerebral cortex.
Exposed to a forced walking stress for 2 weeks, some rats became persistently inactive (depression-model rats), whereas others gradually recovered from exhaustion (spontaneous recovery rats). We also studied rats exposed to short-term stress, rats without stress, and the model rats treated with imipramine or saline. We examined the density of noradrenergic axons in the frontal cortex using retrograde labeling of the locus coeruleus with horseradish peroxidase injected into the cortex and immunohistochemical staining of cortical axons with dopamine beta-hydroxylase antiserum. The density was significantly lower in the depression-model rats, but tended to be higher in the recovery rats and short-term stressed rats. Chronic treatment with imipramine significantly increased the density in the model rats. There was also a correlation between the density of noradrenergic axons and the recovery rate of activity. Our results suggest that cortical noradrenergic degeneration is involved in the pathogenesis of depression.
Kitayama
I
I
Department of Psychiatry, Mie University School of Medicine, Japan.
Yaga
T
T
Kayahara
T
T
Nakano
K
K
Murase
S
S
Otani
M
M
Nomura
J
J
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001369:Axons / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects* / Q000503:physiopathology; D003866:Depressive Disorder / Q000503:physiopathology; D004195:Disease Models, Animal; D005625:Frontal Lobe / Q000187:drug effects / Q000503:physiopathology; D007099:Imipramine / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008125:Locus Coeruleus / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000503:physiopathology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013315:Stress, Psychological / Q000150:complications* / Q000503:physiopathology
D018759:Adrenergic Uptake Inhibitors; D007099:Imipramine; D009638:Norepinephrine