Behavioral activation in rats requires endogenous ascorbate release in striatum

Ascorbate (vitamin C) is found in high concentrations in the striatum in wh ich it may play a role in behavioral activation. To test this hypothesis, f reely behaving rats received bilateral intrastriatal infusions of ascorbate oxidase (AAO) to inactivate extracellular ascorbate. Slow-scan voltammetry was used simultaneously to assess changes in ascorbate and 3,4-dihydroxyph enylacetic acid (DOPAC), a major dopamine metabolite, near the infusion sit e. Intrastriatal AAO, but not saline vehicle, caused a rapid decline in bot h ascorbate and behavioral activation. Within 20 min, an ascorbate loss of 50-70% led to a near-total inhibition of all recorded behavior, including o pen-field locomotion, approach of novel objects, and social interactions wi th other rats. DOPAC levels remained stable, arguing against an AAO-induced disruption of dopamine transmission. Consistent with this interpretation, subsequent injection of 1.0 mg/kg d-amphetamine, an indirect dopamine agoni st, quickly restored behavioral activation, which also was accompanied by a marked rise in extracellular ascorbate. Bilateral AAO infusions into dorsa l hippocampus, which also has a high level of extracellular ascorbate, fail ed to alter behavioral activation, indicating that a loss of brain ascorbat e per se does not suppress behavior. Collectively, these results implicate ascorbate in the behavioral operations of the striatum and suggest that the extracellular level of this vitamin plays a critical role in behavioral ac tivation.