Miele, Maddalena and Mura, Maria A. and Enrico, Paolo and Esposito, Giovanni and Serra, Pier Andrea and Migheli, Rossana and Zangani, Danilo and Miele, Egidio (2000) On the mechanism of d-amphetamine-induced changes in glutamate, ascorbic acid and uric acid release in the striatum of freely moving rats. British Journal of Pharmacology, Vol. 129 (3), p. 582-588. eISSN 1476-5381. Article.
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1 The effects of systemic, intrastriatal or intranigral administration of d-amphetamine on glutamate, aspartate, ascorbic acid (AA), uric acid, dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in dialysates from the striatum 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 concentrations 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 those of glutamate, AA uric acid or 5-HIAA, over a 2 h period after d-amphetamine. Haloperidol (0.1 mM), given intrastriatally, increased aspartate concentrations without affecting those of glutamate or AA. 4 d-Amphetamine (0.2 mM), given intranigrally, increased AA and uric acid dialysate 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 sites. The changes in aspartate levels may be evoked by at least two mechanisms: striatal (mediated by inhibitory dopaminergic receptors) and nigral (activation of amino acid carrier-mediated uptake.
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