Estrogen modulates 5-HT 1A agonist inhibition of lordosis behavior but not binding of [ 3H]-8-OH-DPAT

Abstract

Previous studies showed that repeated estrogen treatment reduces the ability of the 5-HT 1A receptor agonist, 8-hydroxy-2(di- n-propylamino) tetralin (8-OH-DPAT), to inhibit lordosis behavior of female rats. The present study evaluated the effects of repeated estrogen treatment on lordosis behavior and 5-HT 1A receptor binding and coupling to G protein in the hypothalamus-preoptic area using the agonist ligand [ 3H]-8-OH-DPAT, which binds selectively to G-protein-coupled 5-HT 1A receptors. Rats were injected twice with 25 or 50 μg of estradiol benzoate (EB) 7 days apart followed by 500 μg of progesterone (P) 48 h after the second EB injection. Controls received a single injection of 25 or 50 μg EB followed 48 h later by 500 μg of P. Four hours after P, 0.15 mg/kg 8-OH-DPAT was injected, and lordosis behavior examined for 30 min. Rats treated twice with EB showed significantly less 8-OH-DPAT inhibition of lordosis behavior than rats receiving a single EB injection. For receptor binding, rats received EB without P treatment. None of the estrogen treatments reduced [ 3H]-8-OH-DPAT binding density or affinity in the hypothalamus-preoptic area or hippocampus. These studies suggest that estrogen modulates 5-HT 1A agonist potency without a measurable change in 5-HT 1A receptor density or coupling to G protein.