Opposite morphological responses of partially denervated cortical serotonergic and noradrenergic axons to repeated stress in adult rats

We examined plastic changes in serotonin (5-HT) axons following repeated stress in the adult rat brain, and compared stress-induced changes between 5-HT and noradrenaline (NA) axons. We locally injected the specific neurotoxin to 5-HT axons or to NA axons into the frontal cortex to cause partial denervation. The animals were mildly restrained from 1 day after the neurotoxin injection and this stress was repeated daily for 20 min during the first 2 days and for 40 min during the next 11 days. On the fourteenth day after injection, the brains were removed to visualize 5-HT and NA axons by immunohistochemistry. Repeated stress did not significantly alter the denervation area of 5-HT or NA axons, but the density of 5-HT axons was increased whereas that of NA axons was decreased in cortical regions outside the denervation site. In addition, the expression of brain-derived neurotrophic factor (BDNF) was increased in cortical regions where the 5-HT axon density was increased in response to stress. These results suggest that repeated stress causes opposite changes in the morphology of partially denervated 5-HT and NA axons in the cerebral cortex. The stress-induced increase in BDNF expression may contribute to 5-HT axon sprouting following repeated stress.