Gulley J M, Rebec G V
Department of Psychology, Indiana University, Bloomington 47405, USA.
Pharmacol Biochem Behav. 1999 May;63(1):125-9. doi: 10.1016/s0091-3057(98)00249-4.
Pretreatment with ascorbate, a modulator of dopamine transmission in the striatum, enhances the ability of haloperidol, a dopamine antagonist, to induce catalepsy and block the motor-activating effects of amphetamine. The present study extended this line of work to a lever-release version of the conditioned avoidance response (CAR) task, which is highly sensitive to changes 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/kg, IP) or vehicle was tested either alone or in conjunction with haloperidol (0.01 and 0.05 mg/kg, SC). Compared to vehicle pretreatment, 1000 mg/kg ascorbate alone or in combination with haloperidol impaired CAR performance by increasing avoidance latency. Latency to escape footshock was not impaired, ruling out a generalized motor deficit. In contrast, 100 mg/kg ascorbate alone or in combination with haloperidol had no consistent effects on CAR performance, even at a haloperidol dose (0.005 mg/kg, SC) known to potentiate dopamine transmission by preferentially blocking autoreceptors. Collectively, these results support an antidopaminergic action of ascorbate on striatal function, but suggest that this effect requires relatively high systemic doses.
抗坏血酸是纹状体中多巴胺传递的调节剂，用其进行预处理可增强多巴胺拮抗剂氟哌啶醇诱导僵住症的能力，并阻断苯丙胺的运动激活作用。本研究将这一系列工作扩展至条件性回避反应（CAR）任务的杠杆释放版本，该任务对纹状体多巴胺的变化高度敏感。成年雄性大鼠接受训练，通过在音调开始后的500毫秒内释放杠杆来避免足部电击。单独或与氟哌啶醇（0.01和0.05毫克/千克，皮下注射）联合测试抗坏血酸（100和1000毫克/千克，腹腔注射）或赋形剂。与赋形剂预处理相比，1000毫克/千克的抗坏血酸单独使用或与氟哌啶醇联合使用，通过增加回避潜伏期损害了CAR表现。逃避足部电击的潜伏期未受损害，排除了全身性运动缺陷。相比之下，100毫克/千克的抗坏血酸单独使用或与氟哌啶醇联合使用，即使在已知通过优先阻断自身受体来增强多巴胺传递的氟哌啶醇剂量（0.005毫克/千克，皮下注射）下，对CAR表现也没有一致的影响。总体而言，这些结果支持抗坏血酸对纹状体功能的抗多巴胺能作用，但表明这种作用需要相对较高的全身剂量。
