Chronic haloperidol produces a time- and dose-related slowing of lick rhythm in rats: implications for rodent models of tardive dyskinesia and neuroleptic-induced parkinsonism
Chronic haloperidol produces a time- and dose-related slowing of lick rhythm in rats: implications for rodent models of tardive dyskinesia and neuroleptic-induced parkinsonism
复制标题
DOI：
10.1007/s002130050592
复制
发表时间：
1998-05-01
影响因子：
3.4
通讯作者：
Wang, GH
中科院分区：
文献类型：
--
作者：
Fowler, SC;Wang, GH
为了研究慢性氟哌啶醇对大鼠口腔运动功能的影响，我们用这种典型的抗精神病药物连续给药102d，同时记录每天舔水时的舌运动动力学(最大力值、舔节奏、舔次数)。在长期服用氟哌啶醇后(车辆，0.06。0.12，0.24 mg/kg)，连续给药32天，每隔2天或3天连续给药一次，观察胆碱能(东莨菪碱：0.05~0.20 mg/kg；苯海索：0，15~1.0 mg/kg)或5-羟色胺(利坦色林：0.5~4.0 mg/kg；喹帕嗪：0.5~4.0 mg/kg)探针药物对氟哌啶醇引起的小鼠舔食行为改变的拮抗作用。氟哌啶醇呈剂量依赖性地减少峰值力量和舔舔次数，在开始治疗的2或3天内效果明显。氟哌啶醇对舔食节律的显著影响最早出现在第13天，并在剩余的处理期间逐渐增加。东莨菪碱、苯海索和喹帕嗪减少了氟哌啶醇对至少一种舔食行为的影响。在7天的氟哌啶醇停药期间，四个剂量组的所有舌部动力学指标都是相似的。总体而言，结果显示出帕金森样和迟发性运动障碍样效应共同出现的特征。
In order to characterize the development of orolingual motor effects of chronic haloperidol treatment in rats, this typical neuroleptic was administered for 102 days while daily measurements of tongue movement dynamics (peak force, lick rhythm, number of licks) during water Licking were recorded. After chronic haloperidol dosing (vehicle, 0.06. 0.12, 0.24 mg/kg for four separate groups) for 32 days and continuing every second or third day of the chronic dosing period, the effects of cholinergic (scopolamine: 0.05-0.20 mg/kg; trihexyphenidyl: 0,15-1.0 mg/kg) or serotonergic (ritanserin: 0.5-4.0 mg/kg; quipazine: 0.5-4.0 mg/kg) probe drugs were examined for their capacity to antagonize the alterations in licking behavior induced by haloperidol. Haloperidol dose-dependently reduced peak force and number of licks, effects which were apparent within 2 or 3 days of the start of treatment. Significant effects of haloperidol on lick rhythm first emerged on day 13 and gradually increased in magnitude through the remaining treatment period. Scopolamine, trihexyphenidyl, and quipazine reduced haloperidol's effects on at least one measure of licking behavior. During a 7-day haloperidol withdrawal period, the four dosage groups were similar on all measures of tongue dynamics. Overall, the results exhibited features suggesting the co-occurrence of Parkinson-like and tardive dyskinesia-like effects.