Effect of direct and indirect dopamine agonists on brain extracellular ascorbate levels in the striatum and nucleus accumbens of awake rats.
Systemic administration of direct and indirect dopamine agonists resulted in increased extracellular ascorbic acid levels in the striatum and, to a lesser degree, in the nucleus accumbens as measured by in vivo voltammetry. Intraperitoneal d-amphetamine sulfate (5mg/kg) increased ascorbate concentrations in striatal extracellular fluid. Amphetamine also increased extracellular ascorbate levels in the nucleus accumbens although more gradually and to a lesser extent. Intraperitoneal phenethylamine hydrochloride (20 mg/kg) following pargyline hydrochloride pretreatment (20 mg/kg) increased extracellular ascorbate levels in the striatum significantly above the small increase seen in the nucleus accumbens. The direct acting dopamine agonists Ly-141865 and Ly-163502 when given i.p. at 1 mg/kg, resulted in increased extracellular ascorbate concentrations in both brain areas, again with a significantly greater effect in the striatum. These results indicate that brain extracellular ascorbate levels can be modulated by dopaminergic neuro-transmission and that this modulation is quantitatively different in different dopamine-containing brain structures.
Phebus
L A
LA
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285.
Roush
M E
ME
Clemens
J A
JA
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004873:Ergolines / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains
D015259:Dopamine Agents; D004873:Ergolines; D010627:Phenethylamines; D011804:Quinolines; D019257:Quinpirole; C029261:phenethylamine; D001205:Ascorbic Acid; D003913:Dextroamphetamine; C047726:quinelorane