PT  - JOURNAL ARTICLE
AU  - Cabrera, T M
AU  - Battaglia, G
TI  - Delayed decreases in brain 5-hydroxytryptamine2A/2C receptor density and function in male rat progeny following prenatal fluoxetine.
DP  - 1994 May 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 637--645
VI  - 269
IP  - 2
4099  - http://jpet.aspetjournals.org/content/269/2/637.short
4100  - http://jpet.aspetjournals.org/content/269/2/637.full
SO  - J Pharmacol Exp Ther1994 May 01; 269
AB  - 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.