The origin of circadian and amphetamine-induced changes in the extracellular concentration of brain ascorbate.

Circadian and amphetamine-induced changes in the extracellular concentration of ascorbate in the striatum and hippocampus of unrestrained rats were measured voltammetrically; the amphetamine-induced changes in striatal ascorbate were confirmed using a push-pull perfusion technique. Circadian changes in the level of blood plasma ascorbate, and the distribution of [(14)C]ascorbate after the intraperitoneal administration of amphetamine were also measured. Circadian changes in brain and plasma ascorbate levels were 6 h out of phase. Amphetamine caused little change in the distribution of blood-borne ascorbate in the striatum or hippocampus. These results suggest that changes in extracellular ascorbate levels in the brain are not secondary to changes in the supply of ascorbate from the blood; they arise from the modulation in ascorbate release from, and/or the uptake into, neuropil.