title: Effects of risperidone and paliperidone pre-treatment on locomotor response following prenatal immune activation.
abstract: OBJECTIVE
  Limited 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.
  
  
  METHODS
  Pregnant 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.
  
  
  RESULTS
  Risperidone 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.
  
  
  CONCLUSIONS
  Risperidone 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.
authors: Cincinnati Veterans Affairs Medical Center, Psychiatry Service (V116A), Cincinnati, OH 45220, USA. neil.richtand@uc.edu
authors: Neil M
authors: NM
authors: Richtand
authors: Rebecca
authors: R
authors: Ahlbrand
authors: Paul
authors: P
authors: Horn
authors: Kevin
authors: K
authors: Stanford
authors: Stefanie L
authors: SL
authors: Bronson
authors: Robert K
authors: RK
authors: McNamara
mesh_terms: D000661:Amphetamine / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000697:Central Nervous System Stimulants; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D007555:Isoxazoles / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D000068882:Paliperidone Palmitate; D011070:Poly I-C / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology*; D012559:Schizophrenia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D007555:Isoxazoles; D011743:Pyrimidines; D000661:Amphetamine; D018967:Risperidone; D011070:Poly I-C; D000068882:Paliperidone Palmitate