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Donepezil differentially interacts with gonadal hormones in male rats responding under a multiple schedule of repeated acquisition and performance
Author(s) -
Leonard Stuart T.,
Hearn John K.,
Winsauer Peter J.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.941.9
Subject(s) - donepezil , testosterone (patch) , hormone , endocrinology , medicine , estrogen , cholinergic , acetylcholinesterase , gonadal hormones , psychology , chemistry , dementia , castration , enzyme , biochemistry , disease
Gonadal steroid hormones can mediate learning and memory, presumably by enhancing the functional status of cholinergic neurons. In contrast to the effects of estrogen in female rats, some evidence suggests that testosterone in male rats may decrease acetylcholine levels, and thus, the activity of the cholinergic system. The present study investigated the interactive effects of testosterone and donepezil, an acetylcholinesterase inhibitor, in subjects responding under a multiple schedule of repeated acquisition and performance of response chains. Donepezil dose‐effect curves (0.56‐10 mg/kg) were determined in males that were gonadally intact, gonadectomized, gonadectomized with testosterone replacement, or gonadectomized with estradiol replacement. For all four groups, donepezil produced dose‐dependent rate‐decreasing and error‐increasing effects in both the acquisition and performance components. Gonadally intact, GX, and GX+T males showed less disruption of response rate in both the acquisition and performance components than GX+E males. In terms of accuracy, GX+E males had the highest percentage of mean errors after control injections and also after donepezil administration in both the acquisition and performance components. Together, these data demonstrate that donepezil differentially interacts with gonadal hormones, and estrogen in particular, in male rats. Supported by DA 019625.