Lesions of cholinergic forebrain nuclei: changes in avoidance behavior and scopolamine actions.

The acquisition of active (shuttle-box) and passive avoidance conditioned responses and the effects of scopolamine on acetylcholine (ACh) output in freely moving rats and on conditioned responses were investigated 20 days after placing a unilateral lesion in the magnocellular forebrain nuclei (MFN). In the lesioned rats spontaneous ACh output from the cerebral cortex ipsilateral to the lesion was slightly decreased, while on the other hand the increase in ACh output elicited by scopolamine was strongly reduced. Sham operated rats always performed more active avoidance responses than MFN lesioned rats in the daily training shuttle-box sessions, and the facilitating effect of scopolamine (1 mg/kg IP) on the shuttle-box performance was suppressed. However the lesion did not disrupt the shuttle-box performance whenever training had taken place before the lesion. In the lesioned rats retested 30 min after the training trial, an impairment of the passive avoidance response was found. The effect of the lesion was potentiated by scopolamine. The results show therefore that MFN lesions impair the cortical cholinergic mechanisms, whose activity seems to play an important role in cognitive functions.