As previously reported, 6-hydroxydopamine (6-OHDA) lesions to the region of the nucleus accumbens blocked the locomotor activation induced by low doses of d-amphetamine, and produced a supersensitive locomotor response to the dopamine (DA) agonist, apomorphine. This same lesion, however, failed to block the locomotor activation induced by scopolamine or caffeine. These results suggest that scopolamine and caffeine activate locomotion in the rat by acting independently of presynaptic terminals in the mesolimbic DA system.