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