Simple disturbance of the dam in the neonatal period can alter haloperidol-induced catalepsy in the adult offspring

Abstract

Three experiments were performed to determine whether apparently minimal disturbances of dams and litters would influence haloperidol-induced akinesia. In Experiment I, Long-Evans hooded rats (a) were left unmanipulated, (b) received nestcage relocation and observation, (c) received nestcage relocation/observation and maternal separation, or (d) received nestcage relocation/observation and pup handling. The male adult offspring received open-field testing and later received forepaw-on-dowel catalepsy testing following saline, morphine (20 mg/kg), or haloperidol (2 mg/kg). In Experiment II, hooded rats received (a) no manipulation, (b) nestcage relocation, (c) maternal separation, or (d) pup handling. At weaning, dams were tested in the open-field. Activity wheel locomotion of the offspring was assessed following saline or haloperidol for 3 days/week for 3 weeks; then, 5 and 7 days later, rats received haloperidol (0.5 mg/kg) and catalepsy testing. In both experiments, manipulations involving the dam reduced the offsprings' haloperidol-induced catalepsy, but, in Experiment II, a history of haloperidol administration distinguished between the effects of nestcage relocation and maternal separation. In Experiment III, Swiss albino mice received (a) no treatment, (b) nestcage relocation and maternal separation, (c) relocation/separation and mild cold stress of pups, (d) relocation/separation and pup handling, or (e) relocation/separation and severe cold stress of pups. Adult male mice received saline or haloperidol (2.5 mg/kg) and inclined grid catalepsy testing. Mice receiving relocation/separation and mice receiving relocation/separation and severe cold stress showed enhanced catalepsy versus control mice. Thus, it was concluded that seemingly innocuous events in infancy can influence the intensity of extrapyramidal side effects of neuroleptics in adulthood.