Acute and long-term amphetamine treatments alter extracellular ascorbate in neostriatum but not nucleus accumbens of freely moving rats

The ability of amphetamine to alter the extracellular level of ascorbate, an apparent modulator of neostriatal function, was assessed voltammetrically in the neostriatum and nucleus accumbens of awake, behaving rats. Whereas acute administration (1.0 and 5.0 mg/kg d-amphetamine) produced a dose-dependent rise in neostriatal ascorbate, there was no change in the nucleus accumbens. Vehicle injections had no significant effect on ascorbate levels in either location. Administration of 5.0 mg/kg d-amphetamine for one week enhanced neostriatal ascorbate release even further, but this effect returned to acute levels when treatment continued for a second week. Multiple amphetamine injections for up to two weeks failed to alter extracellular ascorbate in the nucleus accumbens. The results of these experiments confirm a site-specific action of amphetamine on ascorbate release and suggest complex changes in the extracellular level of this substance in the neostriatum with long-term treatment.