We have further studied the effects of neonatal ventral hippocampal lesions on DA-related behaviors such as apomorphine-induced hyperlocomotion and stereotypy, catalepsy, and prepulse inhibition of a startle response. Our results extended our previous findings that rats with neonatal excitotoxic damage do not express abnormal behavioral changes related to the mesolimbic/nigrostriatal DA system before the age of puberty, but that their responsiveness to DA-related behavioral manipulations is exaggerated after puberty. We also studied the role sexual maturation in emergence of these behavioral disturbances. Our results indicate that the mechanism of the delayed emergence of these behavioral disturbances. Our results indicate that the mechanism of the delayed emergence of abnormal behaviors is not dependent upon gonadal hormones. We also investigated the effectiveness of neuroleptic treatment in rats with hippocampal damage. Haloperidol (0.1-0.4 mg/kg) and clozapine (4 mg/kg) administered for 3 weeks suppressed spontaneous locomotor hyperactivity in lesioned animals. Only haloperidol, however, produced supersensitive response to apomorphine 5 days post treatment. This effect was observed in lesioned but not in control animals. These data indicate that both typical and atypical neuroleptics normalize hyperactivity in lesioned rats, and that treatment with a typical neuroleptic may induce more profound withdrawal effects in lesioned than in neurologically intact animals. As we studied the effects of this experimental hippocampal lesion as a potential animal model of schizophrenia, we were also interested in its effects on memory function that is known to be impaired in this illness. Our results show that spatial memory is impaired at an early age followings neonatal hippocampal damage, and that it neither improves nor deteriorates over time.
