On the mechanism of d-amphetamine-induced changes in glutamate, ascorbic acid and uric acid release in the striatum of freely moving rats

1 The effects of systemic, intrastriatal or intranigral administration of d -amphetamine on glutamate, aspartate, ascorbic acid (AA), uric acid, dopami ne (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5- hydroxyindoleacetic acid (5-HIAA) concentrations in dialysates from the str iatum of freely-moving rats were evaluated using microdialysis. 2 d-Amphetamine (2 mg kg(-1)) given subcutaneously (s.c.) increased DA, AA and uric acid and decreased DOPAC + HVA, glutamate and aspartate dialysate concentrations over a 3 h period after d-amphetamine, 5-HIAA concentrations were unaffected. Individual changes in glutamate and AA dialysate concentr ations were negatively correlated. 3 d-Amphetamine (0.2 mM), given intrastriatally, increased DA and decreased DOPAC + HVA and aspartate dialysate concentrations, but failed to change t hose of glutamate. AA uric acid or 5-HIAA, over a 2 h period after d-amphet amine. Haloperidol (0.1 mM), given intrastriatally, increased aspartate con centrations without affecting those of glutamate or AA. 4 d-Amphetamine (0.2 mM), given intranigrally, increased AA and uric acid d ialysate concentrations and decreased those of glutamate, aspartate and DA; DOPAC + HVA and 5-HIAA concentrations were unaffected. 5 These results suggest that d-amphetamine-induced increases in AA and uric acid and decreases in glutamate concentrations are triggered at nigral sit es. The changes in aspartate levels may be evoked by at least two mechanism s: striatal (mediated by inhibitory dopaminergic receptors) and nigral (act ivation of amino acid carrier-mediated uptake).