Effects of long-term haloperidol treatment on glutamate-evoked ascorbate release in rat striatum

Repeated haloperidol injections increase extracellular striatal ascorbate. Because ascorbate release depends on glutamate uptake, we assessed this mechanism in the haloperidol effect. Linear staircase voltammetry was combined with intrastriatal infusions of L- or D-glutamate or saline in behaving rats after 7 or 21 days of haloperidol (0.5 mg/kg, s.c.). Control animals, receiving either vehicle or no treatment, responded to L-, but not D-glutamate or saline infusion with a 50% increase in ascorbate. In contrast, glutamate-evoked ascorbate release disappeared after 7 but reappeared after 21 days of haloperidol. Thus, increased striatal ascorbate release following chronic haloperidol cannot be explained by an enhanced response to glutamate. (C) 2001 Elsevier Science B.V. All rights reserved.