Unilateral kainate lesions of the neostriatum and 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle were used to assess the role of neostriatal and ascending dopaminergic neurons, respectively, on dopamine-agonist induced release of neostriatal ascorbate as measured voltammetrically in freely moving rats. Electrochemically modified, carbon-fiber electrodes recorded the effects of direct (a combination of 10 mg/kg SKF-38393 and 1.0 mg/kg quinpirole) as well as indirect (2.5 mg/kg D-amphetamine or 20.0 mg/kg GBR-12909) dopamine agonists. Relative to controls, kainate, but not 6-OHDA, lesions abolished the ability of both direct and indirect dopamine agonists to induce neostriatal ascorbate release. These results suggest that unlike dopaminergic afferents, neostriatal output pathways play a critical role in the modulation of neostriatal ascorbate levels.