Estrogen enhances potassium-stimulated acetylcholine release in the rat hippocampus.

Short-term estrogen replacement has been shown to enhance basal forebrain cholinergic function. Whether or not long-term estrogen replacement can enhance basal forebrain cholinergic function has been questioned in light of recent studies showing that several cholinergic measures which are increased following short-term treatment are not increased following longer-term (>30 days) treatment. In the present study, in vivo microdialysis was used to assess the effects of continuous estradiol replacement on basal forebrain cholinergic function. Our data show that 6-7 weeks of continuous estradiol replacement significantly enhanced potassium-stimulated acetylcholine release in the hippocampus of ovariectomized rats, and that this effect was reversed following discontinuation of the estrogen treatment. These data are consistent with the hypothesis that estrogen-mediated effects on cholinergic neurons can contribute to the effects of long-term estrogen replacement on cognitive performance recently described.