title: Risperidone pretreatment prevents elevated locomotor activity following neonatal hippocampal lesions.
abstract: Long-standing behavioral abnormalities emerge after puberty in rats following neonatal hippocampal lesion, providing a developmental model of abnormal rat behavior that may have predictive validity in identifying compounds effective in treating symptoms of schizophrenia. We sought to test the predictive validity of the neonatal hippocampal lesion model in identifying preventive treatment for first-episode psychosis. We determined the effect of risperidone, recently studied for prevention of first-episode psychosis, on the development of elevated locomotor activity following neonatal hippocampal lesions. Rat pups received hippocampal or sham lesions on postnatal day 7, followed by treatment with risperidone or vehicle from postnatal days 35 to 56. Locomotor activity in response to novelty, amphetamine, and nocturnal locomotion were determined on postnatal day 57. Low-dose risperidone (45 microg/kg) pretreatment prevented elevated locomotor activity in some, but not all, of the behavioral tasks following neonatal hippocampal lesions. In contrast, higher risperidone pretreatment was less effective in preventing elevated locomotor activity following neonatal hippocampal lesions. Because low risperidone dosages were also found to be effective in preventing first-episode psychosis in human studies, these data support the predictive validity of the hippocampal lesion model in identifying medications for prevention of first-episode psychosis. Additionally, these data support the use of low-dose risperidone in psychosis prevention, and suggest the possibility that higher risperidone doses could be less effective in this application.
authors.affiliation: Cincinnati Veterans Affairs Medical Center, Psychiatry Service (V116A), Cincinnati, OH, USA. neil.richtand@uc.edu
authors.forename: Neil M
authors.initials: NM
authors.lastname: Richtand
authors.forename: Benjamin
authors.initials: B
authors.lastname: Taylor
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Welge
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ahlbrand
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Ostrander
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Burr
authors.forename: Scott
authors.initials: S
authors.lastname: Hayes
authors.forename: Lique M
authors.initials: LM
authors.lastname: Coolen
authors.forename: Laurel M
authors.initials: LM
authors.lastname: Pritchard
authors.forename: Aaron
authors.initials: A
authors.lastname: Logue
authors.forename: James P
authors.initials: JP
authors.lastname: Herman
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002940:Circadian Rhythm / Q000187:drug effects; D018891:Dentate Gyrus / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007051:Ibotenic Acid / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology*
chemical_list: D014150:Antipsychotic Agents; D018765:Dopamine Uptake Inhibitors; D018690:Excitatory Amino Acid Agonists; D007051:Ibotenic Acid; D000661:Amphetamine; D018967:Risperidone