{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T20:02:46Z","timestamp":1790971366498,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cholinesterase inhibitors with distinct pharmacological profiles may influence exploratory behavior, yet their effects on recall-related exploration in physiologically intact animals remain insufficiently characterized. The present study aimed to directly compare the effects of donepezil, a relatively selective acetylcholinesterase inhibitor, and tacrine, a cholinesterase inhibitor with broader enzymatic and pharmacological activity, on exploratory allocation during memory recall in healthy rats. Male Wistar rats were assigned to five groups (n = 8\/group): control, donepezil 1 mg\/kg, donepezil 3 mg\/kg, tacrine 3 mg\/kg, and tacrine 5 mg\/kg. Treatments were administered intraperitoneally 50 min before the acquisition trial, while recall performance was evaluated 24 h later without additional treatment using a two-trial Y-maze paradigm. Time spent and entries into the familiar and novel arms, novel-to-familiar ratios, and mean time per entry were analyzed. Control animals showed no marked preference for the novel arm, whereas donepezil produced only limited, non-significant behavioral changes. Tacrine 5 mg\/kg significantly increased the U\/K time ratio compared with controls (p = 0.0006) and the U\/K entry ratio (p = 0.001), primarily through reduced time spent in the familiar arm (p = 0.0004) and fewer familiar-arm entries (p = 0.025). Absolute time spent in, and entries into, the novel arm did not differ significantly among groups (p = 0.689 and p = 0.883, respectively). Overall, these findings suggest that tacrine, but not donepezil, modified recall-phase exploratory preference in healthy rats, predominantly by reducing persistence in the familiar arm.<\/jats:p>","DOI":"10.3390\/biom16081102","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T11:45:26Z","timestamp":1785239126000},"page":"1102","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differential Effects of Donepezil and Tacrine on Recall-Phase Exploratory Behavior in Healthy Male Wistar Rats: A Two-Trial Y-Maze Study"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7936-827X","authenticated-orcid":false,"given":"Adrian-Florentin","family":"Dragomir","sequence":"first","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2874-1674","authenticated-orcid":false,"given":"Smaranda","family":"Stoleru","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2475-3646","authenticated-orcid":false,"given":"Aurelia Cristiana","family":"Barbu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurelian","family":"Zugravu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6218-5389","authenticated-orcid":false,"given":"Maria Carina","family":"Dumitrescu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miruna Valeria","family":"Moraru","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurentiu-Nicolae","family":"Ciuca","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Fratea","sequence":"additional","affiliation":[{"name":"Service Anesthesie-Reanimation, Groupe Hospitalier de la Piti\u00e9-Salp\u00eatri\u00e8re, CEDEX 13, 75651 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9489-1750","authenticated-orcid":false,"given":"Claudia Elena","family":"Dobre","sequence":"additional","affiliation":[{"name":"Faculty of Midwifery and Nursing, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara Maria","family":"Stoleru","sequence":"additional","affiliation":[{"name":"Faculty of Medical Engineering, National University of Science and Technology Politehnica Bucharest, 060042 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana Andreia","family":"Coman","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ion","family":"Fulga","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/jnc.14052","article-title":"Cholinergic modulation of the hippocampal region and memory function","volume":"142","author":"Haam","year":"2017","journal-title":"J. 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