Donepezil and tacrine differentially interact with estradiol in female rats responding under a multiple schedule of repeated acquisition and performance

Abstract

In females, ovarian hormones can facilitate learning and memory processes but such beneficial effects are often lost or diminished following long‐term hormone deprivation. Because the absence of estradiol disrupts learning and memory presumably by reducing the activity of the cholinergic system, acetylcholinesterase (AchE) inhibitors may reverse this disruption by enhancing the functional status of the cholinergic system. This study investigated the interactive effects of estrogen and two AchE inhibitors, donepezil (0.56–5.6 mg/kg) and tacrine (0.56–10 mg/kg), in subjects responding under a multiple schedule of repeated acquisition and performance of response chains. Dose‐effect curves were determined in female rats that were gonadally intact, ovariectomized, or ovariectomized with estradiol replacement. In all three groups, both drugs produced dose‐dependent rate‐decreasing and error‐increasing effects in the acquisition and performance components. However, OVX females were less sensitive to the error‐increasing effects of donepezil in the acquisition component and the error‐increasing effects of tacrine in the performance component. These data extend the current knowledge regarding the effects of estrogen on nonspatial learning and memory tasks, and help determine if estradiol's capacity for mediating responding on such tasks is related to its ability to affect cholinergic neurotransmission. Supported by DA019625 and Contract NSF(2010)‐PFUND‐198 Board of Regents of Louisiana