Robson_2026_Psychopharmacology.(Berl)__

RATIONALE: Cholinergic signalling is critical for attentional control and signal detection, yet the contribution of specific acetylcholine receptor (AChR) subtypes remains poorly understood. Although the alpha7 nicotinic AChR (nAChR) holds promise as a target for cognition-enhancing therapy, clinical findings to date have been inconsistent. OBJECTIVE: To investigate the effects of putative cognitive enhancing drugs, including those targeting cholinergic transmission and alpha7 nAChRs on a visual signal detection task (SDT). METHODS: 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 alpha7 nAChR antagonist (MLA), an alpha7 nAChR PAM (CCMI), and an alpha7 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'), the latter reflecting subjects' ability to discriminate signal from noise. RESULTS: High dose mecamylamine impaired d' and hit rate and slowed responding. Galantamine significantly improved d' at moderate doses but not when a distractor was present. MLA produced dose-dependent improvements in d' that were preserved under distraction. In contrast, positive allosteric modulation and activation of alpha7 nAChRs impaired task performance. Scopolamine produced marked behavioural slowing, whereas VU0467154 and tolcapone did not reliably affect d'. CONCLUSIONS: These findings demonstrate that alpha7 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.