title: Premarin improves memory, prevents scopolamine-induced amnesia and increases number of basal forebrain choline acetyltransferase positive cells in middle-aged surgically menopausal rats.
abstract: Conjugated equine estrogen (CEE) is the most commonly prescribed estrogen therapy, and is the estrogen used in the Women's Health Initiative study. While in-vitro studies suggest that CEE is neuroprotective, no study has evaluated CEE's effects on a cognitive battery and brain immunohistochemistry in an animal model. The current experiment tested whether CEE impacted: I) spatial learning, reference memory, working memory and long-term retention, as well as ability to handle mnemonic delay and interference challenges; and, II) the cholinergic system, via pharmacological challenge during memory testing and ChAT-immunoreactive cell counts in the basal forebrain. Middle-aged ovariectomized (Ovx) rats received chronic cyclic injections of either Oil (vehicle), CEE-Low (10 microg), CEE-Medium (20 microg) or CEE-High (30 microg) treatment. Relative to the Oil group, all three CEE groups showed less overnight forgetting on the spatial reference memory task, and the CEE-High group had enhanced platform localization during the probe trial. All CEE groups exhibited enhanced learning on the spatial working memory task, and CEE dose-dependently protected against scopolamine-induced amnesia with every rat receiving the highest CEE dose maintaining zero errors after scopolamine challenge. CEE also increased number of ChAT-immunoreactive neurons in the vertical diagonal band of the basal forebrain. Neither the ability to remember after a delay nor interference, nor long-term retention, was influenced by the CEE regimen used in this study. These findings are similar to those reported previously for 17 beta-estradiol, and suggest that CEE can provide cognitive benefits on spatial learning, reference and working memory, possibly through cholinergic mechanisms.
authors.affiliation: Department of Psychology, Arizona State University, Tempe, AZ 85287, USA.
authors.forename: Jazmin I
authors.initials: JI
authors.lastname: Acosta
authors.forename: Loretta
authors.initials: L
authors.lastname: Mayer
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Talboom
authors.forename: Cynthia
authors.initials: C
authors.lastname: Zay
authors.forename: Melissa
authors.initials: M
authors.lastname: Scheldrup
authors.forename: Jonathan
authors.initials: J
authors.lastname: Castillo
authors.forename: Laurence M
authors.initials: LM
authors.lastname: Demers
authors.forename: Craig K
authors.initials: CK
authors.lastname: Enders
authors.forename: Heather A
authors.initials: HA
authors.lastname: Bimonte-Nelson
mesh_terms: D000647:Amnesia / Q000139:chemically induced* / Q000517:prevention & control* / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects; D004958:Estradiol / Q000097:blood; D004966:Estrogens, Conjugated (USP) / Q000494:pharmacology*; D004970:Estrone / Q000097:blood; D005260:Female; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D018727:Muscarinic Antagonists; D009929:Organ Size; D016548:Prosencephalon / Q000201:enzymology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012601:Scopolamine; D012741:Sexual Maturation / Q000502:physiology*; D014599:Uterus / Q000033:anatomy & histology / Q000502:physiology
chemical_list: D003278:Contraceptives, Oral, Hormonal; D004966:Estrogens, Conjugated (USP); D018727:Muscarinic Antagonists; D004970:Estrone; D004958:Estradiol; D012601:Scopolamine; D002795:Choline O-Acetyltransferase