Chronic administration of haloperidol during development: Later psychopharmacological responses to apomorphine and arecoline

Abstract

Offspring of pregnant rats injected with 0.25 mg/kg of haloperidol or saline throughout gestation and until weaning were psychopharmacologically tested for their responsiveness to arecoline and apomorphine. On postnatal day 50, offspring of such chronic treatments were tested in the open field after administration of 0, 0.05, 0.1, 1.0 or 3.0 mg/kg apomorphine, a dopamine agonist. The two chronic treatment groups did not differ in response to high doses of apomorphine which induced stereotyped sniffing and a depression of matrix crossing behavior. However, while control offspring exhibited a low dose (0.05 mg/kg apomorphine) suppression of matrix crossings and rearing behavior, haloperidol treated offspring did not, which may indicate a functional hyposensitivity of dopaminergic autoreceptors in these treated animals. When tested at postnatal day 65 for their cataleptic responses to the cholinergic agonist arecoline, haloperidol treated offspring were more cataleptic to 2 and 5 mg/kg arecoline than control offspring. This suggests that chronic dopamine receptor blockade during development may have long-term indirect effects on the sensitivity of the cholinergic system.