Enhancement of learning four weeks after stimulation of the nucleus locus coeruleus in the rat: differential effects of dorsal noradrenergic bundle lesion and lesion of the locus coeruleus proper.

In previous studies we showed that electrical stimulation of the nucleus locus coeruleus produced, four weeks later, a significant improvement in performance in acquisition of food-reinforced operant conditioning. In the two experiments reported here, we tested the role of the dorsal noradrenergic bundle and of the locus coeruleus proper in this long-term effect. Lesioning the dorsal noradrenergic bundle did not have a clear and consistent effect, whereas lesion of the nucleus coeruleus proper suppressed almost totally the beneficial effect of the stimulation. In the first experiment, the dorsal noradrenergic bundle was lesioned by local bilateral injection of 6-hydroxydopamine, 8 days before stimulation of the locus coeruleus. Four weeks after the stimulation, the rats were tested for acquisition of the operant task. Three control groups were used: not lesioned but stimulated, lesioned but not stimulated, and not lesioned/not stimulated. The locus coeruleus stimulation produced the same improvement of performance at the beginning of the acquisition, whether or not the dorsal noradrenergic bundle had been lesioned. However, a significant decrement of performance was observed in lesioned and stimulated rats during the last 40 min of the acquisition. In the second experiment, the locus coeruleus proper was destroyed by bilateral local injection of 6-hydroxydopamine and the locus coeruleus region was stimulated 15 days later. Three control groups were used, as in the first experiment. All the rats were tested 4 weeks later for acquisition of the operant task. The locus coeruleus lesion significantly attenuated the beneficial effect of the stimulation; however, the performance of the lesioned and stimulated rats was still significantly superior to that of the lesioned but not stimulated rats. These results suggest that the noradrenergic locus coeruleus system is involved in the long-term effect, but that the rostral projections passing through the dorsal bundle, in front of the lesion, are not critically involved in the observed effect.