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Although the \u03b17 nicotinic AChR (nAChR) holds promise as a target for cognition-enhancing therapy, clinical findings to date have been inconsistent.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the effects of putative cognitive enhancing drugs, including those targeting cholinergic transmission and \u03b17 nAChRs on a visual signal detection task (SDT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male and female Sprague Dawley rats were trained on an SDT. Cholinergic transmission was probed systemically with nicotinic and muscarinic receptor antagonists (mecamylamine and scopolamine), a cholinesterase inhibitor (galantamine), an M4-AChR positive allosteric modulator (PAM; VU0467154), an \u03b17 nAChR antagonist (MLA), an \u03b17 nAChR PAM (CCMI), and an \u03b17 nAChR partial agonist (SSR-180,711). Catecholaminergic transmission was probed using the catechol-O-methyltransferase (COMT) inhibitor tolcapone. A novel, trial-level signal detection theory-based generalised linear mixed-effects model (SDT-GLMM) was used to index response bias and perceptual sensitivity (d\u2032), the latter reflecting subjects\u2019 ability to discriminate signal from noise.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High dose mecamylamine impaired d\u2032 and hit rate and slowed responding. Galantamine significantly improved d\u2032 at moderate doses but not when a distractor was present. MLA produced dose-dependent improvements in d\u2032 that were preserved under distraction. In contrast, positive allosteric modulation and activation of \u03b17 nAChRs impaired task performance. Scopolamine produced marked behavioural slowing, whereas VU0467154 and tolcapone did not reliably affect d\u2032.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings demonstrate that \u03b17 nAChR modulation bidirectionally and dose-dependently regulates perceptual sensitivity, irrespective of attentional distraction. These findings have implications for targeted cognitive enhancement in disorders of attention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00213-026-07169-7","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:58:34Z","timestamp":1790063914000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Modulatory effects of \u03b17-nicotinic cholinergic receptors on perceptual sensitivity in a visual signal detection task"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0334-2793","authenticated-orcid":false,"given":"Harry J.","family":"Robson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8482-0764","authenticated-orcid":false,"given":"Alexander R.H.","family":"Matthews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-9025-8671","authenticated-orcid":false,"given":"Livia J.F.","family":"Wilod Versprille","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-064X","authenticated-orcid":false,"given":"Johann","family":"du Hoffmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2282-3660","authenticated-orcid":false,"given":"Jeffrey W.","family":"Dalley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"7169_CR1","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1152\/physrev.00015.2008","volume":"89","author":"EX Albuquerque","year":"2009","unstructured":"Albuquerque EX, Pereira EFR, Alkondon M, Rogers SW (2009) Mammalian Nicotinic Acetylcholine Receptors: From Structure to Function. 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KG, Germany. HJR was funded by a studentship from Boehringer Ingelheim Pharma GmbH & Co. KG, Germany and the Medical Research Council, UK. LJFWV was funded by a Cambridge Trust studentship at Cambridge University, Prins Bernhard Cultuurfonds and VSBfonds from the Netherlands and by an Angharad Dodds John Fellowship at Downing College, Cambridge. ARHM was funded by a Woolf Fischer Trust studentship and the Cambridge Trusts.","order":3,"name":"Ethics","label":"<b>Competing interests<\/b>","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third-party material in this article are included in the article\u2019s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article\u2019s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit\n                      \n                      .","order":4,"name":"Ethics","label":"<b>Open Access<\/b>","group":{"name":"EthicsHeading","label":"Declarations"}}]}}