M. Miele et al., On the mechanism of d-amphetamine-induced changes in glutamate, ascorbic acid and uric acid release in the striatum of freely moving rats, BR J PHARM, 129(3), 2000, pp. 582-588
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).