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


OBJECTIVE
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.


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.
Norcross
Maxine
M
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.
Mathur
Poonam
P
Poonam
Mathur
M
Enoch
Abigail J
AJ
Karlsson
Rose-Marie
RM
Brigman
Jonathan L
JL
Cameron
Heather A
HA
Harvey-White
Judith
J
Holmes
Andrew
A
D000367:Age Factors; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001143:Arousal / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D005239:Fear / Q000187:drug effects*; D005473:Fluoxetine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000097:blood; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009042:Motivation; D009043:Motor Activity / Q000187:drug effects; D012701:Serotonin / Q000097:blood; D012931:Social Environment; D013045:Species Specificity
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D003345:Corticosterone