Abstract
We have previously demonstrated that rats with neonatal excitotoxic hippocampal damage manifest abnormal dopamine (DA)-related behaviors after puberty, a phenomenon that has implications for an animal model of schizophrenia. In this study we investigated the effects of subchronic treatment with haloperidol and clozapine in these animals. The ventral hippocampus (VH) of rat pups was lesioned with ibotenic acid on postnatal day 7 (PD7). Starting at PD56, rats were treated for 21 days with either vehicle (VEH), haloperidol (HAL) (0.1 mg/kg, IP), or clozapine (CLOZ) (4 mg/kg, IP). Spontaneous locomotor activity was measured 0.5 hour after the last injection. Apomorphine (APO)-induced stereotypy and locomotion were evaluated five days later. The VH lesioned rats treated with VEH expressed enhanced novelty- and apomorphine-induced hyperlocomotion, as well as potentiated apomorphine-induced stereotypic behaviors as compared to sham-lesioned counterparts. Spontaneous locomotor activity was suppressed by haloperidol but not by clozapine in the sham-operated group, whereas both drugs were effective in suppressing hyperlocomotion in the VH lesioned rats. Withdrawal supersensitivity to apomorphine was seen in the haloperidol but not in the clozapine-treated lesioned rats, and none of the drugs produced significant supersensitivity in the sham-operated animals. These results indicate that the two neuroleptics exerted differential behavioral effects in neurologically intact and hippocampally lesioned animals, and that these effects were also drug-specific.
Similar content being viewed by others
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lipska, B., Weinberger, D. Subchronic Treatment with Haloperidol and Clozapine in Rats with Neonatal Excitotoxic Hippocampal Damage. Neuropsychopharmacol 10, 199–205 (1994). https://doi.org/10.1038/npp.1994.22
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/npp.1994.22
Keywords
This article is cited by
-
Toward early estimation and treatment of addiction vulnerability: radial arm maze and N-acetyl cysteine before cocaine sensitization or nicotine self-administration in neonatal ventral hippocampal lesion rats
Psychopharmacology (2016)
-
Neurodegenerative Aspects in Vulnerability to Schizophrenia Spectrum Disorders
Neurotoxicity Research (2014)
-
Risperidone Pretreatment Prevents Elevated Locomotor Activity Following Neonatal Hippocampal Lesions
Neuropsychopharmacology (2006)
-
Neonatal Ventral Hippocampal Lesions Produce an Elevation of ΔFosB-Like Protein(s) in the Rodent Neocortex
Neuropsychopharmacology (2006)