Fluoxetine and aripiprazole treatment following prenatal immune activation exert longstanding effects on rat locomotor response

• Published in: Physiology & behavior 2012-05, Vol.106 (2), p.171-177
• Main Authors: Richtand, Neil M, Ahlbrand, Rebecca, Horn, Paul, Tambyraja, Rabindra, Grainger, Molly, Bronson, Stefanie L, McNamara, Robert K
• Format: Article
• Language: English
• Subjects: Acute-Phase Reaction - chemically induced; Acute-Phase Reaction - complications; Adult and adolescent clinical studies; adverse effects; amphetamine; Amphetamine - pharmacology; Animal model; Animals; antidepressants; Antipsychotic Agents - adverse effects; Antipsychotic Agents - pharmacology; Antipsychotic Agents - therapeutic use; Aripiprazole; Behavioral psychophysiology; Biological and medical sciences; Disease Models, Animal; Dopamine; Dose-Response Relationship, Drug; drug therapy; Female; Fluoxetine - adverse effects; Fluoxetine - pharmacology; Fluoxetine - therapeutic use; Fundamental and applied biological sciences. Psychology; Immune System - drug effects; Male; Maternal; Medical sciences; mice; Motor Activity - drug effects; Neuropharmacology; Pharmacology. Drug treatments; Piperazines - adverse effects; Piperazines - pharmacology; Piperazines - therapeutic use; Poly I-C - pharmacology; Pregnancy; Prenatal Exposure Delayed Effects - psychology; progeny; 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; Psychology. Psychophysiology; Psychopathology. Psychiatry; Psychopharmacology; Psychoses; Psychosis; Quinolones - adverse effects; Quinolones - pharmacology; Quinolones - therapeutic use; Rats; Rats, Sprague-Dawley; risk; Schizophrenia; Schizophrenia - chemically induced; Schizophrenia - complications; Schizophrenia - drug therapy; Serotonin; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use; youth development
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2012.02.004

Abstract Aim Studies characterizing treatment interventions in a naturalistic setting suggest that antidepressant and antipsychotic medications may be equally effective in improving clinical outcome in individuals at high risk for first-episode psychosis. Of interest, both beneficial as well as potentially adverse effects have been observed following fluoxetine treatment in a mouse prenatal immune activation model of relevance to psychosis prevention. We sought to extend those findings by examining the effects of fluoxetine, as well as the antipsychotic medication aripiprazole, in a rat prenatal immune activation model. 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 fluoxetine (10.0 mg/kg/d), aripiprazole (0.66 mg/kg/d), or vehicle from postnatal days 35 to 70. Locomotor responses to novelty, saline injection, and amphetamine (1 and 5 mg/kg) were determined at three months, i.e., 21 days following drug discontinuation. Results Both fluoxetine and aripiprazole had beneficial 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. Significantly, both drugs also exerted effects in offspring of control (saline-treated) dams on locomotor response to injection. Conclusions Fluoxetine and aripiprazole pretreatment of poly I:C offspring from postnatal days 35 to 70 stabilized response to amphetamine exposure persisting through 3 months of age, similar to earlier findings in mice that fluoxetine treatment following prenatal immune activation prevented altered locomotor response to amphetamine. The current data also confirm earlier findings of potential adverse behavioral effects in offspring of control dams following treatment with fluoxetine and antipsychotic medications, highlighting the potential for both therapeutic as well as safety concerns with exposure to preventive pharmacological treatments over the course of adolescent development. Further study is needed to determine clinical and epidemiological consequences of these pre-clinical findings.