6-Hydroxydopamine lesion of the rat prefrontal cortex increases locomotor activity, impairs acquisition of delayed alternation tasks, but does not affect uninterrupted tasks in the radial maze.

The role of mesocortical dopamine neurons in locomotion and acquisition of various delayed and uninterrupted maze tasks was investigated in the rat. Dopaminergic terminals of the medial prefrontal cortex were lesioned by stereotaxically guided injections of the selective neurotoxin 6-hydroxydopamine (6-OHDA), while noradrenergic neurons were protected by systemically administered desipramine. 6-OHDA lesions resulted in a selective depletion of dopamine and its metabolite, dihydroxyphenylacetic acid, in the prefrontal cortex but not in subcortical structures. Prefrontal serotonin was not depleted. 6-OHDA-cloned rats performed uninterrupted alternation tasks (spontaneous and reinforced alternation) in the radial maze in the same manner as controls, whereas performance of delayed alternation in the T-maze and the radial maze was impaired in lesioned rats. In addition, locomotor activity during maze performance was increased in lesioned rats. Based on the hypothesis that increased motor activity and impaired delayed alternation performance are due to increased susceptibility to interfering stimuli, we propose tentatively that prefrontal dopamine may function to suppress interference during the delay period of certain cognitive tasks.