Effects of risperidone and paliperidone pre-treatment on locomotor response following prenatal immune activation |
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Authors: | Richtand Neil M Ahlbrand Rebecca Horn Paul Stanford Kevin Bronson Stefanie L McNamara Robert K |
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Institution: | a Cincinnati Veterans Affairs Medical Center, Psychiatry Service (V116A), 3200 Vine Street, Cincinnati, OH 45220, United States b Department of Psychiatry, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML0583, Cincinnati, OH 45267, United States c Neuroscience Graduate Program, University of Cincinnati, Cincinnati, OH 45267, United States d Department of Mathematical Sciences, University of Cincinnati, Cincinnati, OH 45221, United States |
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Abstract: | AimLimited data are available regarding pharmacological characteristics of effective interventions for psychosis prevention. Enrollment challenges in psychosis prevention trials impede screening diverse interventions for efficacy. Relevant animal models could help circumvent this barrier. We previously described prevention with risperidone of abnormal behavior following neonatal hippocampal lesion. We aimed to extend those findings evaluating risperidone and paliperidone following prenatal immune activation, a developmental model of a schizophrenia risk factor. We evaluated a later developmental time point to determine persistent effects of drug treatment.MethodsPregnant Sprague-Dawley rats were injected with poly I:C or saline on gestational day 14. Offspring of poly I:C and saline-treated dams received risperidone (0.45 mg/kg/d), paliperidone (0.05 mg/kg/d), or vehicle from postnatal days 35-70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following antipsychotic discontinuation.ResultsRisperidone and paliperidone had persistent effects on behavioral response to amphetamine (1 mg/kg) at 3 months, ameliorating the impact of prenatal immune activation on offspring of poly I:C-treated dams. Risperidone, but not paliperidone, also exerted persistent effects in offspring of saline-treated dams on locomotor response to saline and amphetamine (5 mg/kg) injection.ConclusionsRisperidone and paliperidone pre-treatment of poly I:C offspring during peri-pubertal development stabilized response to amphetamine exposure persisting into early adulthood. Prenatal immune activation provides a model for evaluating effects of an environmental risk factor for schizophrenia, and has potential utility for identifying pharmacological approaches to early intervention. |
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Keywords: | Maternal Schizophrenia Animal model First-episode psychosis Prodrome Dopamine |
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