Subchronic treatment with haloperidol and clozapine in rats with neonatal excitotoxic hippocampal damage.
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.
Lipska
B K
BK
Clinical Brain Disorders Branch, National Institute of Mental Health, NIH, Washington, DC 20032.
Weinberger
D R
DR
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001058:Apomorphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D005260:Female; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects*; D007051:Ibotenic Acid / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009498:Neurotoxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D013239:Stereotyped Behavior / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D009498:Neurotoxins; D011954:Receptors, Dopamine; D007051:Ibotenic Acid; D003024:Clozapine; D006220:Haloperidol; D001058:Apomorphine