Effects of risperidone and paliperidone pre-treatment on locomotor response following prenatal immune activation

• Published in: Journal of psychiatric research 2011-09, Vol.45 (9), p.1194-1201
• Main Authors: Richtand, Neil M, Ahlbrand, Rebecca, Horn, Paul, Stanford, Kevin, Bronson, Stefanie L, McNamara, Robert K
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Amphetamine - adverse effects; Amphetamines; Animal model; Animals; Animals, Newborn; Antenatal; Antipsychotic Agents - pharmacology; Biological and medical sciences; Central Nervous System Stimulants; Dams; Disease Models, Animal; Dopamine; Drug Interactions; Female; First-episode psychosis; Immune response; Isoxazoles - pharmacology; Maternal; Medical sciences; Motor Activity - drug effects; Neuropharmacology; Paliperidone Palmitate; Pharmacology. Drug treatments; Poly I-C - immunology; Pregnancy; Prenatal Exposure Delayed Effects - physiopathology; Prevention; Prodrome; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Pyrimidines - pharmacology; Rats; Rats, Sprague-Dawley; Risperidone; Risperidone - pharmacology; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - etiology; Schizophrenia - physiopathology; Time Factors
• ISSN: 0022-3956; 1879-1379
• DOI: 10.1016/j.jpsychires.2011.02.007

Abstract Aim 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.