title: Estradiol treatment and its interaction with the cholinergic system: effects on cognitive function in healthy young women.
abstract: The steroid hormone estradiol has been shown to modulate cognitive function in both animals and humans, and although the exact mechanisms associated with these effects are unknown, interactions with the cholinergic system have been proposed. We examined the neurocognitive effects of short-term estradiol treatment and its interaction with the cholinergic system using the muscarinic receptor antagonist scopolamine in healthy young women. Thirty-four participants (Mean age+/-SD=22.4+/-4.4) completed baseline cognitive assessment and then received either 100 microg/day transdermal estradiol or transdermal placebo for 31 days. On days 28 and 31 of treatment, further cognitive assessment was performed pre- and 90 min post-scopolamine (0.4 mg) or placebo (saline) injection, under a randomized double-blind placebo-controlled design. Short-term estradiol treatment significantly enhanced spatial working memory with a trend for improvement in long-term verbal learning and memory. Overall, estradiol treatment did not protect against or attenuate the scopolamine-induced impairments in the cognitive domains assessed. Findings suggest that estrogen has minimal effects on cholinergic-mediated cognitive processes following short-term treatment. Effects of estradiol treatment may be dependent on age, dose of estradiol, integrity of cholinergic innervation and baseline endogenous estrogen levels, which may in part explain the inconsistent findings in the literature.
authors.affiliation: Brain Sciences Institute, Faculty of Life and Social Sciences, Swinburne University of Technology, VIC, Australia. cali.bartholomeusz@mh.org.au
authors.forename: Cali F
authors.initials: CF
authors.lastname: Bartholomeusz
authors.forename: Keith A
authors.initials: KA
authors.lastname: Wesnes
authors.forename: Jayashri
authors.initials: J
authors.lastname: Kulkarni
authors.forename: Luis
authors.initials: L
authors.lastname: Vitetta
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Croft
authors.forename: Pradeep J
authors.initials: PJ
authors.lastname: Nathan
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D000328:Adult; D001288:Attention / Q000187:drug effects; D018678:Cholinergic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004347:Drug Interactions; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006262:Health; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects; D010919:Placebos; D012601:Scopolamine / Q000008:administration & dosage / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018678:Cholinergic Agents; D018680:Cholinergic Antagonists; D010919:Placebos; D004958:Estradiol; D012601:Scopolamine