Abstract
Rationale
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.
Objectives
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.
Results
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.
Conclusions
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.
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Acknowledgements
The research is supported by the Intramural Research Program of the National Institute of Alcohol Abuse and Alcoholism (Z01-AA000411) and National Institute on Mental Health (Z01-MH002784). The authors declare no financial conflicts of interest.
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Maxine Norcross and Poonam Mathur contributed equally to this work.
An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-008-1297-2
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Norcross, M., Poonam, M., Enoch, A.J. et al. Effects of adolescent fluoxetine treatment on fear-, anxiety- or stress-related behaviors in C57BL/6J or BALB/cJ mice. Psychopharmacology 200, 413–424 (2008). https://doi.org/10.1007/s00213-008-1215-7
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DOI: https://doi.org/10.1007/s00213-008-1215-7