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大鼠产前和产后早期接触氟哌啶醇行为后果的比较评估。

Comparative evaluation of the behavioural consequences of prenatal and early postnatal exposure to haloperidol in rats.

作者信息

Cuomo V, Cagiano R, Renna G, Serinelli A, Brunello N, Racagni G

出版信息

Neurobehav Toxicol Teratol. 1985 Sep-Oct;7(5):489-92.

PMID:3841192
Abstract

The intensity of apomorphine (1-2 mg/kg)-induced stereotyped behaviour was significantly lower in 60 day old offspring of rats treated with haloperidol during pregnancy (0.5 mg/kg SC for 15 days, beginning on day 4 after conception) than in vehicle-exposed animals. Moreover, at 60 days of age, apomorphine (1-2 mg/kg)-induced inhibition of locomotor activity was much less marked in haloperidol-pretreated than in vehicle-pretreated rats. Conversely, our previous data showed that behavioural supersensitivity to apomorphine (1-2 mg/kg) was still present 40 days after the last administration of haloperidol, if the animals received the drug (0.5 mg/kg SC) from birth to 20 days of age. Finally, at 80 days of age, animals prenatally exposed to haloperidol were subjected to a differential reinforcement of low rates schedule (DRL-15 sec). The results indicate that the acquisition of the DRL task performance criterion (Rs/Rf less than or equal to 2.5) was significantly more rapid in control animals than in haloperidol-pretreated rats. In this regard, we previously showed that early postnatal exposure to the neuroleptic also impairs the acquisition of the DRL schedule in adult rats. These data confirm and extend the differences in behavioural consequences of prenatal and early postnatal exposure to haloperidol, and further point to the usefulness of DRL task in the evaluation of subtle behavioural changes induced by psychotropic drugs in the absence of overt signs of neurotoxicity.

摘要

与接受赋形剂处理的动物相比,孕期接受氟哌啶醇治疗(从受孕后第4天开始,皮下注射0.5mg/kg,持续15天)的大鼠60日龄后代中,阿扑吗啡(1-2mg/kg)诱导的刻板行为强度显著降低。此外,在60日龄时,阿扑吗啡(1-2mg/kg)诱导的运动活动抑制在氟哌啶醇预处理的大鼠中比在赋形剂预处理的大鼠中表现得要轻得多。相反,我们之前的数据表明,如果动物从出生到20日龄接受氟哌啶醇(0.5mg/kg皮下注射),在最后一次给药氟哌啶醇40天后,对阿扑吗啡(1-2mg/kg)的行为超敏反应仍然存在。最后,在80日龄时,对产前暴露于氟哌啶醇的动物进行低速率差异强化程序(DRL-15秒)测试。结果表明,与氟哌啶醇预处理的大鼠相比,对照动物达到DRL任务表现标准(Rs/Rf小于或等于2.5)的速度要快得多。在这方面,我们之前表明,出生后早期暴露于该抗精神病药物也会损害成年大鼠对DRL程序的习得。这些数据证实并扩展了产前和出生后早期暴露于氟哌啶醇在行为后果上的差异,并进一步指出了DRL任务在评估精神药物在无明显神经毒性迹象时诱导的细微行为变化中的有用性。

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