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Abstract
Fluoxetine (FLX), a selective serotonin reuptake inhibitor, is prescribed for the
treatment of major depressive disorder in young populations. Here, we explore the
short- and long-term consequences of adolescent exposure to FLX on behavioral reactivity
to emotion-eliciting stimuli.
Adolescent male rats received FLX (10 mg/kg) twice daily for 15 consecutive days (postnatal
days 35-49). The influence of FLX on behavioral reactivity to rewarding and aversive
stimuli was assessed 24 hours (short-term) or 3 weeks after FLX treatment (long-term).
A separate group of adult rats was also treated with FLX (postnatal days 65-79) and
responsiveness to forced swimming was assessed at identical time intervals as with
the adolescents.
Fluoxetine exposure during adolescence resulted in long-lasting decreases in behavioral
reactivity to forced swimming stress and enhanced sensitivity to sucrose and to anxiety-eliciting
situations in adulthood. The FLX-induced anxiety-like behavior was alleviated by re-exposure
to FLX in adulthood. Fluoxetine treatment during adolescence also impaired sexual
copulatory behaviors in adulthood. Fluoxetine-treated adult rats did not show changes
in behavioral reactivity to forced swim stress as observed in those treated during
adolescence and tested in adulthood.
Treating adolescent rats with FLX results in long-lived complex outputs regulated
by the emotional valence of the stimulus, the environment in which it is experienced,
and the brain circuitry likely being engaged by it. Our findings highlight the need
for further research to improve our understanding of the alterations that psychotropic
exposure may induce on the developing nervous system and the potential enduring effects
resulting from such treatments.
Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights
reserved.