Document Detail

Long-term effects of fluoxetine or vehicle administration during pregnancy on behavioral outcomes in guinea pig offspring.
MedLine Citation:
PMID:  15365684     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Assessment of the benefits versus risks associated with antidepressant use during pregnancy must include an analysis of possible drug effects on fetal development. Human studies indicate that prenatal fluoxetine exposure is associated with adverse neonatal outcomes. Animal modeling may provide useful information concerning possible long-term effects of prenatal fluoxetine exposure. Limitations in previous such studies using rat models may be overcome using a guinea pig model in which fluoxetine is delivered by osmotic pump throughout pregnancy. METHODS: Initial experiments measured the half-life of fluoxetine and dosing required to achieve human therapeutic blood levels in the guinea pig. In subsequent experiments, guinea pigs received fluoxetine or vehicle via osmotic pump or no treatment throughout pregnancy. Outcome measures included: pregnancy characteristics, weight gain, and, in offspring as adults, pain threshold, acoustic startle responses and prepulse inhibition. RESULTS: There was no effect of treatment group on gestation length, number of live-births or still-births, maternal or offspring weight gain, and acoustic startle responses. In adult offspring, pain threshold was decreased by vehicle treatment during gestation. Prenatal fluoxetine increased pain threshold, relative to vehicle controls. Prepulse inhibition of startle was increased in adult offspring treated prenatally with either vehicle or fluoxetine compared to no treatment. CONCLUSIONS: The guinea pig provides a practicable and clinically relevant model of prenatal fluoxetine exposure. Adult guinea pigs exposed to fluoxetine prenatally showed increased thermal pain thresholds but no change in prepulse inhibition, indicating selective long-term effects of prenatal fluoxetine on serotonin-modulated behaviors. Further studies on long-term effects of prenatal fluoxetine on nociception are warranted.
Raphael Vartazarmian; Saima Malik; Glen B Baker; Patricia Boksa
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-09-10
Journal Detail:
Title:  Psychopharmacology     Volume:  178     ISSN:  0033-3158     ISO Abbreviation:  Psychopharmacology (Berl.)     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-18     Completed Date:  2005-09-12     Revised Date:  2010-03-23    
Medline Journal Info:
Nlm Unique ID:  7608025     Medline TA:  Psychopharmacology (Berl)     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  328-38     Citation Subset:  IM    
Department of Psychiatry, Douglas Hospital Research Center, McGill University, 6875 LaSalle Boulevard, Verdun, QC, Canada, H4H 1R3.
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MeSH Terms
Disease Models, Animal
Fluoxetine / administration & dosage,  pharmacokinetics,  toxicity*
Guinea Pigs
Pain Threshold / drug effects
Prenatal Exposure Delayed Effects*
Serotonin Uptake Inhibitors / administration & dosage,  pharmacokinetics,  toxicity
Startle Reaction / drug effects
Reg. No./Substance:
0/Serotonin Uptake Inhibitors; 54910-89-3/Fluoxetine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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