Delayed decreases in brain 5-hydroxytryptamine2A/2C receptor density and function in male rat progeny following prenatal fluoxetine.
The present study investigated the consequences of prenatal exposure to the 5-hydroxytryptamine (serotonin; 5-HT) uptake inhibitor fluoxetine on central 5-HT2A/2C receptors and receptor-mediated function in male and female progeny. Pregnant rats were administered saline or fluoxetine (10 mg/kg s.c.) daily from gestational day 13 through 20. All litters were fostered to non-treated lactating dams. Fluoxetine did not alter weight gain during pregnancy but did significantly decrease progeny weight at birth (-8%) and at postnatal day (PD) 70 (-14%). Progeny were tested at PD28 (males and females) and PD70 (males) by measuring: 1) (+/-)-[125I]4-iodo,2,5-dimethoxyphenylisopropylamine ([125I]DOI)-labeled 5-HT2A/2C receptors; 2) [3H]paroxetine-labeled 5-HT uptake sites; and 3) the stimulation of adrenocorticotropin, corticosterone and renin after a single injection of the 5-HT2A/2C agonist DOI (2 mg/kg s.c.) to provide an index of 5-HT2A/2C receptor function. At PD28, neither 5-HT2A/2C receptor density nor 5-HT2A/2C receptor-mediated endocrine responses were altered by prenatal exposure to fluoxetine. In contrast, at PD70, the maximal density of hypothalamic 5-HT2A/2C receptors was reduced significantly (-35%) in male progeny of fluoxetine-treated dams. Consistent with the reduction of 5-HT2A/2C receptors, the adrenocorticotropin response to DOI was attenuated markedly and selectively (-58%; P < .05) in PD70 progeny following prenatal exposure to fluoxetine. Basal levels of all hormones measured were unaffected by prenatal fluoxetine. Likewise, fluoxetine did not alter the number of hypothalamic 5-HT uptake sites or the binding of [125I]DOI to cortical 5-HT2A/2C receptors.
Cabrera
T M
TM
Department of Pharmacology and Experimental Therapeutics, Loyola University of Chicago, Stritch School of Medicine, Maywood, Illinois.
Battaglia
G
G
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D015430:Weight Gain
D000662:Amphetamines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D005473:Fluoxetine; D000324:Adrenocorticotropic Hormone; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine