Long-term effects of fluoxetine or vehicle administration during pregnancy on behavioral outcomes in guinea pig offspring.
BACKGROUND
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.
Vartazarmian
Raphael
R
Department of Psychiatry, Douglas Hospital Research Center, McGill University, 6875 LaSalle Boulevard, Verdun, QC, Canada, H4H 1R3.
Malik
Saima
S
Baker
Glen B
GB
Boksa
Patricia
P
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D006168:Guinea Pigs; D017288:Pain Threshold / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013216:Reflex, Startle / Q000187:drug effects; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity
D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors