Modulatory effects of ascorbate, alone or with haloperidol, on a lever-release conditioned avoidance response task

Pretreatment with ascorbate, a modulator of dopamine transmission in the st riatum. enhances the ability of haloperidol, a dopamine antagonist, to indu ce catalepsy and block the motor-activating effects of amphetamine. The pre sent study extended this line of work to a lever-release version of the con ditioned avoidance response (CAR) task, which is highly sensitive to change s in striatal dopamine. Adult male rats were trained to avoid footshock by releasing a lever within 500 ms of tone onset. Ascorbate (100 and 1000 mg/k g, IF) or vehicle was tested either alone or in conjunction with haloperido l(0.01 and 0.05 mg/kg, SC). Compared to vehicle pretreatment, 1000 mg/kg as corbate alone or in combination with haloperidol impaired CAR performance b y increasing avoidance latency. Latency to escape footshock was not impaire d, ruling out a generalized motor deficit. In contrast, 100 mg/kg ascorbate alone or in combination with haloperidol had no consistent efects on CAR p erformance, even at a haloperidol dose (0.005 mg/kg, SC) known to potentiat e dopamine transmission by preferentially blocking autoreceptors. Collectiv ely, these results support an antidopaminergic action of ascorbate on stria tal function, but suggest that this effect requires relatively high systemi c doses. (C) 1999 Elsevier Science Inc.