title: Fluoxetine and aripiprazole treatment following prenatal immune activation exert longstanding effects on rat locomotor response.
abstract: OBJECTIVE
  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.
authors.affiliation: Cincinnati Veterans Affairs Medical Center, Psychiatry Service (V116A), 3200 Vine Street, Cincinnati, Ohio 45220, United States. neil.richtand@uc.edu
authors.forename: Neil M
authors.initials: NM
authors.lastname: Richtand
authors.forename: Rebecca
authors.initials: R
authors.lastname: Ahlbrand
authors.forename: Paul
authors.initials: P
authors.lastname: Horn
authors.forename: Rabindra
authors.initials: R
authors.lastname: Tambyraja
authors.forename: Molly
authors.initials: M
authors.lastname: Grainger
authors.forename: Stefanie L
authors.initials: SL
authors.lastname: Bronson
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
mesh_terms: D000210:Acute-Phase Reaction / Q000139:chemically induced / Q000150:complications; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000068180:Aripiprazole; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D007107:Immune System / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D015363:Quinolones / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000661:Amphetamine; D014150:Antipsychotic Agents; D000068180:Aripiprazole; D005473:Fluoxetine; D010879:Piperazines; D011070:Poly I-C; D015363:Quinolones; D017367:Selective Serotonin Reuptake Inhibitors