Duration-dependent effects of repeated restraint stress on cortical projections of locus coeruleus neurons

Using electrophysiological techniques, changes in noradrenergic fiber innervation in the cerebral cortex following repeated stress (restraint in a small cage for either 1 or 6 h daily) were examined by quantifying the density of cortical terminal axons of locus coeruleus (LC) neurons in the rat. After termination of the stress treatment, the single-unit activity of LC neurons was recorded extracellularly under urethane anesthesia, and antidromic activation from 7 cortical points covering nearly the entire cerebral cortex was examined. The percentage of LC neurons activated anti-dromically from the medial frontal cortex was higher in the animals stressed for 1 h daily for 2 weeks. In contrast, the percentage of LC neurons activated antidromically from the cerebral cortex decreased in the animals who received 6 h stress for 2 weeks. These results suggest that stress can cause dual effects, either sprouting or retraction of cortical LC axons depending upon the duration of stress treatment.