Rocha J B, Santos J E, Rocha L K, Kleinpaul E R
Department of Chemistry, CCNE, Federal University of Santa Maria, RS, Brazil.
Pharmacol Toxicol. 1997 Sep;81(3):114-23. doi: 10.1111/j.1600-0773.1997.tb00040.x.
Undernutrition during critical periods of development may cause changes in the behavioural responses of rats to centrally acting drugs. In the present study, the effects of undernutrition during suckling on the behavioural responses of 21-days-old rats to chlorpromazine (0, 2.5, 5, 10 and 20 mg/kg) or haloperidol (0, 0.125, 0.25, 0.5, 1 or 2 mg/kg) were examined. Locomotion was assessed at 1 hr 30 min., 4 hr 30 min., 7 hr 30 min, and 10 hr 30 min., and catalepsy was scored at 3 hr, 6 hr and 9 hr after drug administration. Drug was injected on two consecutive days. On day 1, saline-treated undernourished rats showed significantly greater locomotion activity than did normal rats. The neuroleptic-induced inhibition of locomotor activity in undernourished rats was significantly less than that observed in normal rats from 4 hr 30 min. to 10 hr 30 min. (chlorpromazine) or from 7 hr 30 min. to 10 hr 30 min. (haloperidol). On day 2, a similar trend was observed but only in rats injected with 5 mg/kg chlorpromazine or 0.5, 1, and 2 mg/kg haloperidol. On day 1, the catalepsy scores at 3 hr revealed no significant difference between nutritional groups, but at 6 hr undernourished rats responded significantly less to chlorpromazine or haloperidol. On day 2, undernourished rats were less responsive to neuroleptics than normal rats, but the effect was not so evident as observed on day 1. The present results suggest that the behavioural effects of chlorpromazine and haloperidol are less persistent in undernourished rats, possibly due to differences in drug distribution and elimination, when compared to well-nourished rats.
发育关键期的营养不良可能会导致大鼠对中枢作用药物的行为反应发生变化。在本研究中,检测了哺乳期营养不良对21日龄大鼠对氯丙嗪(0、2.5、5、10和20毫克/千克)或氟哌啶醇(0、0.125、0.25、0.5、1或2毫克/千克)行为反应的影响。在给药后1小时30分钟、4小时30分钟、7小时30分钟和10小时30分钟评估运动能力,并在给药后3小时、6小时和9小时对僵住症进行评分。连续两天注射药物。在第1天,生理盐水处理的营养不良大鼠的运动活动明显高于正常大鼠。从4小时30分钟到10小时30分钟(氯丙嗪)或从7小时30分钟到10小时30分钟(氟哌啶醇),营养不良大鼠中抗精神病药物诱导的运动活动抑制明显低于正常大鼠。在第2天,观察到类似趋势,但仅在注射5毫克/千克氯丙嗪或0.5、1和2毫克/千克氟哌啶醇的大鼠中。在第1天,3小时时僵住症评分在营养组之间无显著差异,但在6小时时,营养不良大鼠对氯丙嗪或氟哌啶醇的反应明显较小。在第2天,营养不良大鼠对抗精神病药物的反应低于正常大鼠,但效果不如第1天明显。目前的结果表明,与营养良好的大鼠相比,氯丙嗪和氟哌啶醇的行为效应在营养不良大鼠中持续时间较短,这可能是由于药物分布和消除的差异所致。