, 200:413 | Cite as

Effects of adolescent fluoxetine treatment on fear-, anxiety- or stress-related behaviors in C57BL/6J or BALB/cJ mice

  • Maxine Norcross
  • Mathur Poonam
  • Abigail J. Enoch
  • Rose-Marie Karlsson
  • Jonathan L. Brigman
  • Heather A. Cameron
  • Judith Harvey-White
  • Andrew Holmes
Original Investigation



5-Hydroxytryptamine (5-HT, serotonin) plays a major role in brain ontogeny. Disruption of 5-HT during early postnatal development produces lasting changes in rodent ‘emotion-related’ behaviors. Adverse effects of treatment with serotonin reuptake inhibitor (SRI) antidepressants have been reported in human adolescents. However, the long-term effects of chronic SRI treatment during adolescence in rodents remain unclear.


The objectives of the study are to assess the effects of fluoxetine treatment throughout the adolescent period in measures of fear-, anxiety- and stress-related endpoints in drug-free adults and to examine these effects in two genetic strains of mice differing in baseline stress- and anxiety-related behaviors and sensitivity to SRIs.

Materials and methods

C57BL/6J and BALB/cJ mice received one of two fluoxetine doses for 4 weeks during adolescence (3–7 weeks old). A separate group of C57BL/6J and BALB/cJ mice received fluoxetine for 4 weeks during adulthood (8–12 weeks old). After a 3-week washout period, mice were tested for anxiety-like behaviors (novel open field, elevated plus-maze), fear conditioning and extinction, and stress-related responses to forced swim, as well as serotonin brain levels.


Adolescent fluoxetine treatment did not increase adult measures of anxiety-, fear- or stress-related behaviors, or brain serotonin levels. The same duration of treatment in adulthood also had no effects on these measures when tested after a 3-week washout period.


In clear contrast with emotion-related abnormalities caused by preadolescent fluoxetine treatment or genetic inactivation of fluoxetine’s pharmacological target, the 5-HT transporter, fluoxetine treatment throughout mouse adolescence did not produce detectable, lasting abnormalities in either “high” or “low anxiety” inbred mouse strains.


Fluoxetine SSRI Antidepressant Mouse Anxiety Fear Depression Stress Development Serotonin 


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Copyright information

© U.S. Government 2008

Authors and Affiliations

  • Maxine Norcross
    • 1
  • Mathur Poonam
    • 1
  • Abigail J. Enoch
    • 1
  • Rose-Marie Karlsson
    • 2
    • 3
  • Jonathan L. Brigman
    • 1
  • Heather A. Cameron
    • 4
  • Judith Harvey-White
    • 5
  • Andrew Holmes
    • 1
  1. 1.Section on Behavioral Science and Genetics, Laboratory for Integrative NeuroscienceNational Institute on Alcohol Abuse and Alcoholism, National Institutes of HealthRockvilleUSA
  2. 2.Laboratory of Translational and Clinical StudiesInstitute on Alcohol Abuse and Alcoholism, NIHBethesdaUSA
  3. 3.Department of Clinical NeuroscienceKarolinska InstituteStockholmSweden
  4. 4.Unit on Neuroplasticity, Mood and Anxiety Disorders ProgramNational Institute of Mental Health, NIHBethesdaUSA
  5. 5.Laboratory for Physiologic StudiesNational Institute on Alcohol Abuse and Alcoholism, NIHRockvilleUSA

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