Document Detail

Teratogenic effects of maternal antidepressant exposure on neural substrates of drug-seeking behavior in offspring.
MedLine Citation:
PMID:  17850417     Owner:  NLM     Status:  MEDLINE    
If neurotransmitter balance is upset in the developing nervous system by exposure to antidepressant drugs, structural and functional hedonic phenotypes of offspring may be affected. In order to test this hypothesis, two groups of pregnant Wistar dams were exposed to vehicle or fluoxetine by implantation on gestational day 14 of osmotic minipumps delivering 0 or 10 mg/kg/day fluoxetine for 14 days. The consequences of perinatal fluoxetine exposure on offspring conflict-exploratory behavior were quantified using the elevated plus-maze on postnatal day (PND) 30. Beginning on PND 60, the reinforcing properties of acutely administered cocaine were examined using a place conditioning procedure. Beginning on PND 90, a subset of rats were implanted with jugular catheters and allowed to acquire self-administration of cocaine in an operant environment. In support of the hedonic modulation hypothesis, perinatal fluoxetine produced a significant decline in both nucleus accumbens cell count (-9%) and serotonin transporter-like immunoreactivity in the raphe nucleus (-35%) on PND 120. In the elevated plus-maze, perinatal fluoxetine exposure decreased (-21%) overall activity. In the place conditioning trial, only the fluoxetine-treated group exhibited a significant place preference for the compartment paired previously with cocaine. In a cocaine self-administration extinction trial, there was a statistically significant increase (350%) in extinction response rate among fluoxetine-exposed offspring. These findings suggest that perinatal exposure to fluoxetine perturbs adult serotonergic neurotransmission and produces a positive hedonic shift for conditioned reinforcing effects of cocaine.
Patrick A Forcelli; Stephen C Heinrichs
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-09-11
Journal Detail:
Title:  Addiction biology     Volume:  13     ISSN:  1369-1600     ISO Abbreviation:  Addict Biol     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-13     Completed Date:  2008-04-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9604935     Medline TA:  Addict Biol     Country:  England    
Other Details:
Languages:  eng     Pagination:  52-62     Citation Subset:  IM    
Department of Psychology, Boston College, USA.
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MeSH Terms
Amygdala / drug effects,  pathology
Animals, Newborn
Antidepressive Agents, Second-Generation / toxicity*
Arousal / drug effects,  physiology
Brain / drug effects*,  pathology
Cell Count
Cocaine-Related Disorders / pathology*
Conditioning, Classical / drug effects,  physiology
Conflict (Psychology)
Exploratory Behavior / drug effects,  physiology
Extinction, Psychological / drug effects,  physiology
Fluoxetine / toxicity*
Immunoenzyme Techniques
Maze Learning / drug effects,  physiology
Nerve Net / drug effects,  pathology
Neurons / drug effects,  pathology
Nucleus Accumbens / drug effects,  pathology
Parietal Lobe / drug effects,  pathology
Prenatal Exposure Delayed Effects*
Raphe Nuclei / drug effects,  physiology
Rats, Wistar
Serotonin Plasma Membrane Transport Proteins / analysis,  drug effects*
Reg. No./Substance:
0/Antidepressive Agents, Second-Generation; 0/Serotonin Plasma Membrane Transport Proteins; 54910-89-3/Fluoxetine

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

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