Serotonergic hyperinnervation of the frontal cortex in an animal model of depression, the bulbectomized rat.
We studied the influence of olfactory bulbectomy in rats on three different parameters of serotonin (5-HT) presynapses, 5-HT transporter density, tryptophan hydroxylase apoenzyme concentration, and the levels of 5-HT and 5-hydroxyindole acetic acid (5-HIAA) in various brain regions. Compared with sham-operated controls, the Bmax values of [3H]paroxetine binding, the apoenzyme concentration of tryptophan hydroxylase and the level of 5-HIAA, and, therefore, the 5-HIAA/5-HT ratio were significantly and selectively increased in the frontal cortex of bulbectomized rats, measured 12 weeks after surgery. The most likely explanation of the concomitant increase in levels of all three markers of 5-HT presynapses in the frontal cortex is an increased density of 5-HT innervation in this remote projection field of the raphe nuclei. It is suggested that the bulbectomy-associated axotomy of 5-HT fibers projecting to the bulb stimulates collateral sprouting and synaptogenesis, especially in the frontal cortex. The resulting 5-HT hyperinnervation must be expected to alter global neuronal activity in this region and to impair the balance of information flow between this and other brain regions, resulting in a multitude of secondary behavioral and neurochemical changes. The frontocortical abnormalities observed by brain imaging studies in the brains of depressed patients may also be explained by a selective 5-HT hyperinnervation of this brain region.
Zhou
D
D
Psychiatric Clinic of the University of Göttingen, Germany.
Grecksch
G
G
Becker
A
A
Frank
C
C
Pilz
J
J
Huether
G
G
D000818:Animals; D001051:Apoenzymes / Q000378:metabolism; D001665:Binding Sites; D001923:Brain Chemistry; D002352:Carrier Proteins / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003866:Depressive Disorder / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009830:Olfactory Bulb / Q000601:surgery*; D017374:Paroxetine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins; D013569:Synapses / Q000378:metabolism*; D014365:Tryptophan Hydroxylase / Q000378:metabolism
D001051:Apoenzymes; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D017374:Paroxetine; D006897:Hydroxyindoleacetic Acid; D014365:Tryptophan Hydroxylase