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 mec hanism in the haloperidol effect. Linear staircase voltammetry was combined with intrastriatal infusions of L- or D-glutamate or saline in behaving ra ts after 7 or 21 days of haloperidol (0.5 mg/kg, s.c.). Control animals, re ceiving either vehicle or no treatment, responded to L-, but not D-glutamat e or saline infusion with a 50% increase in ascorbate. In contrast, glutama te-evoked ascorbate release disappeared after 7 but reappeared after 21 day s of haloperidol. Thus, increased striatal ascorbate release following chro nic haloperidol cannot be explained by an enhanced response to glutamate. ( C) 2001 Elsevier Science B.V. All rights reserved.