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Psychopharmacology (Berl). 2008 Oct;200(3):413-24. doi: 10.1007/s00213-008-1215-7. Epub 2008 Jul 2.

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

Author information

1
Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 5625 Fishers Lane, Room 2N09, Rockville, MD, 20852-9411, USA.

Erratum in

  • Psychopharmacology (Berl). 2008 Oct;200(3):453. Poonam, Mathur [corrected to Mathur, Poonam].

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.

PMID:
18594797
PMCID:
PMC2574726
DOI:
10.1007/s00213-008-1215-7
[Indexed for MEDLINE]
Free PMC Article

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