Psychopharmacology最新文献

{"title":"Triggered temptations: A new procedure to compare reward-seeking behaviour induced by discriminative and conditioned stimuli in rats.","authors":"Mandy Rita LeCocq, Shaghayegh Najafipashaki, Domiziana Casale, Isabel Laplante, Anne-Noël Samaha","doi":"10.1007/s00213-025-06764-4","DOIUrl":"10.1007/s00213-025-06764-4","url":null,"abstract":"<p><strong>Rationale: </strong>Environmental cues guide animals towards resources vital for survival but can also drive maladaptive reward-seeking behaviours, as in gambling and eating disorders. While conditioned stimuli (CSs) are paired with reward delivery after reward-seeking actions, discriminative stimuli (DSs) signal reward availability independently of behaviour.</p><p><strong>Objective: </strong>We introduce a procedure to compare CS and DS effects on reward-seeking behaviour, in the same subjects within a single session.</p><p><strong>Methods: </strong>Female and male Sprague-Dawley rats learned to self-administer sucrose. During each session, DS+ trials signaled that lever pressing would produce sucrose paired with a CS+ , and DS- trials signaled no sucrose and a CS-. Next, in the absence of sucrose, we assessed the ability of the cues to i) reinforce lever pressing and ii) increase sucrose seeking when presented response-independently. We also assessed the effects of the mGlu_2/3 receptor agonist LY379268 and d-amphetamine on cue-induced sucrose seeking.</p><p><strong>Results: </strong>By the end of self-administration training, lever pressing peaked during DS+ trials and dropped during DS- trials. The DS+ was a conditioned reinforcer of sucrose seeking in both sexes, whereas the CS+ was more effective in males. Response-independent presentations of the DS+ invigorated sucrose seeking in both sexes, whereas the CS+ was effective only in males. LY379268 suppressed DS+ -triggered sucrose seeking in females, with no effect in males. D-amphetamine enhanced sucrose seeking non-specifically across cue conditions in males, with no effect in females.</p><p><strong>Conclusions: </strong>Our new trial-based procedure can be used to identify unique and similar mechanisms underlying DS and CS influences on appetitive behaviour.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1811-1832"},"PeriodicalIF":3.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined effects of low-dose caffeine and warm-up music enhance male athletes' performance in simulated Taekwondo combat: a double-blind, randomized crossover trial.","authors":"Slaheddine Delleli, Ibrahim Ouergui, Hamdi Messaoudi, Florin Cazan, Christopher Garrett Ballmann, Luca Paolo Ardigò, Hamdi Chtourou","doi":"10.1007/s00213-025-06766-2","DOIUrl":"10.1007/s00213-025-06766-2","url":null,"abstract":"<p><strong>Rationale: </strong>How caffeine (CAF) intake and warm-up music combination affect male taekwondo athletes' performance during simulated combat is yet unstudied.</p><p><strong>Objective: </strong>This study examined the potential synergistic effects of low dose of CAF and warm-up music on subsequent taekwondo combat outcomes.</p><p><strong>Methods: </strong>In a double-blinded, randomized, crossover study, 16 male taekwondo athletes performed simulated combats under six conditions: (a) control, (b) CAF without music (CAF + NM), (c) placebo without music (PL + NM), (d) CAF with music (CAF + M), (e) PL with music (PL + M), and (f) no supplement with music (NS + M). After warming-up, athletes rated their felt arousal (FAS). Perceived exertion (RPE), feeling scale (FS), FAS, and physical enjoyment (PACES) were determined after combat while mean (HR_mean) and peak (HR_peak) heart rate were determined for each bout. Each combat was analyzed to determine time-motion aspects and technical-tactical skills.</p><p><strong>Results: </strong>CAF + M shortened skip and pause times than CAF and music in single-use (p < 0.05), while extend attack time than other conditions (p < 0.001). Additionally, CAF + M increased attacks and defensive actions above that of single treatment conditions (all p < 0.05). Moreover, CAF + M improved FS and FAS post-combat than the other conditions (p < 0.001) and PACES compared to NS + M, PL + NM and PL + M conditions (p < 0.05). Similarly, CAF + M reduced HR_mean and HR_peak than the other conditions (p < 0.05).</p><p><strong>Conclusion: </strong>Combining low dose of CAF and warm-up music could be an effective strategy to enhance taekwondo combat performance in male athletes.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1845-1858"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The behavioural effects of the serotonin 1A receptor agonist buspirone on cognition and emotional processing in healthy volunteers.","authors":"Alexander L W Smith, Sorcha Hamilton, Susannah E Murphy, Philip J Cowen, Catherine J Harmer","doi":"10.1007/s00213-025-06770-6","DOIUrl":"10.1007/s00213-025-06770-6","url":null,"abstract":"<p><strong>Rationale: </strong>The 5-HT_1A receptor is expressed widely across the brain and is implicated in the mechanism of action of several therapeutics for mood disorders. However, there is limited and contradictory evidence about the role of this receptor in emotional processing and cognition.</p><p><strong>Objectives: </strong>The current study tested the acute effects of a single dose of the 5-HT_1A agonist buspirone (20 mg), on a range of emotional processing (Emotional Test Battery) and cognitive (Auditory Verbal Learning Task (AVLT) and N-back) tasks in healthy, male and female volunteers (N = 62). The study was a randomised, double-blind, placebo controlled, parallel group design.</p><p><strong>Results: </strong>Buspirone reduced accuracy for detection of facial expressions of disgust and increased misclassification of negative facial emotions. It had no significant effects on categorisation or recall of emotionally-valanced words. Buspirone also reduced recall accuracy in the AVLT but had no significant effect in the N-back task. Participants receiving buspirone were more likely to experience nausea, light-headedness and sleepiness.</p><p><strong>Conclusions: </strong>Acute buspirone administration produced a mild impairment in verbal memory and a subtle negative bias in emotional processing in healthy volunteers. These effects are consistent with the mixed effects of buspirone on pre- and post-synaptic 5-HT_1A receptors.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1859-1873"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296846/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of efficacy and safety of dual orexin receptor antagonists lemborexant and daridorexant for the treatment of insomnia: a systematic review and meta-analysis.","authors":"Ming Tang, Ziyi Shen, Peilu Yu, Meiling Yu, Xiaoqiong Tong, Guohui Jiang","doi":"10.1007/s00213-025-06773-3","DOIUrl":"10.1007/s00213-025-06773-3","url":null,"abstract":"<p><strong>Objective: </strong>To systematically evaluate the clinical efficacy of lemborexant (LEM) and daridorexant (DAR) for the treatment of insomnia, including the difference in efficacy and safety.</p><p><strong>Methods: </strong>In this systematic review and meta-analysis, we searched the randomized controlled trials (RCTs) comparing the efficacy and safety of LEM and DAR in patients with insomnia in five databases from database inception to Mar 16, 2024. We evaluate the quality of studies. Besides, we perform the meta-analysis and detect publication bias.</p><p><strong>Results: </strong>A total of 8 RCTs with 5077 patients were included in this study, including 2239 in the LEM treatment group, 1397 in the DAR treatment group, and 1441 in the placebo (PBO) control group. Both LEM and DAR significantly improved sleep outcomes compared to placebo. LEM was more effective in reducing the time of wake after sleep onset (WASO) (MD, -45.15; 95% CI: -51.75 to -38.56; P < 0.001) and improving subjective sleep onset latency (sSOL) (MD, -25.01; 95% CI: -28.58 to -21.44; P < 0.001) than DAR (WASO: MD: -12.6; 95% CI: -18.71 to -6.5; P < 0.001; sSOL: MD, -2.33; 95% CI: -7.1 to 2.45; P = 0.24). In terms of dosing, DAR at 50 mg demonstrated superior efficacy compared to the 5 mg, 10 mg, and 25 mg doses, indicating a dose-dependent effect. The efficacy of LEM was consistent across the 5 mg and 10 mg doses. Safety profiles revealed that DAR (RR, 1.16; 95% CI: 1.03 to 1.29; P = 0.01) treatment was associated with higher rates of treatment-emergent adverse events (TEAEs) compared to placebo, particularly at the 25 mg dose (RR, 1.15; 95% CI: 1.02 to 1.31; P = 0.03), while LEM (RR, 1.21; 95% CI: 0.98 to 1.50; P = 0.08) showed no significant difference in TEAEs rates compared to placebo. However, LEM (RR, 5.62; 95% CI: 2.92 to 10.83; P < 0.001) was associated with a higher risk of somnolence compared to DAR (RR, 1.55; 95% CI: 0.86 to 2.81; P = 0.15). The overall quality of the included studies was moderate to high based on the risk of bias assessment.</p><p><strong>Conclusion: </strong>Both LEM and DAR are effective and generally safe options for the treatment of insomnia, with LEM showing greater efficacy in improving WASO and sSOL. The choice between LEM and DAR should consider individual patient needs, including the risk of daytime drowsiness and other adverse events. Further direct comparative trials are needed to confirm these findings and inform clinical decision-making.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1693-1711"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agonism at mGluR2 receptors reduces dysfunctional checking on a rodent analogue of compulsive-like checking in obsessive compulsive disorder.","authors":"Colin McKenzie, Bart Sloot, Felippe Espinelli Amorim, Trevor W Robbins, Amy L Milton","doi":"10.1007/s00213-025-06774-2","DOIUrl":"10.1007/s00213-025-06774-2","url":null,"abstract":"<p><strong>Rationale: </strong>Obsessive-compulsive disorder (OCD) affects 1-3% of the population. Current therapies, including selective serotonin reuptake inhibitors, are not universally effective in managing OCD. Recent discoveries indicating hyperactivation of key regions within the corticostriatal thalamic circuitry that supports OCD, and alterations in the ratio of glutamate: GABA in regions such as the anterior cingulate cortex, suggest that drugs targeting glutamatergic signalling may be effective in reducing OCD symptoms.</p><p><strong>Objectives: </strong>This study sought to determine whether two drugs targeting metabotropic glutamate receptors could reduce excessive checking behaviour in a rodent analogue of compulsive-like checking in OCD, the Observing Response Task (ORT).</p><p><strong>Methods: </strong>Rats were trained on the ORT and separately classified on a pavlovian autoshaping task to identify the subpopulation of sign-trackers, which show higher levels of excessive checking. Once responding had stabilised, rats received systemic administration of different doses of the mGluR2 positive allosteric modulator AZD-8529 and its vehicle in a Latin square design, and the effects on ORT performance were assessed. Following completion of AZD-8529 dosing, a subset of rats received administration of different doses of the mGluR2/3 agonist LY404039 and its vehicle in a Latin square design, and ORT performance assessed.</p><p><strong>Results: </strong>Both AZD-8529 and LY404039 produced dose-dependent reductions in checking behaviour, including at doses that did not impair generalised measures of task performance.</p><p><strong>Conclusions: </strong>The similarity in effect of AZD-8529 and LY404039 suggests that the capacity of these drugs to reduce checking is mediated by mGluR2s, which may provide a promising target for future treatment development for OCD.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1893-1907"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143773267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin receptors: possible therapeutic targets for psychiatric disorders.","authors":"Shigeyuki Chaki","doi":"10.1007/s00213-025-06767-1","DOIUrl":"10.1007/s00213-025-06767-1","url":null,"abstract":"<p><strong>Rationale: </strong>Orexins, comprising orexin-A and orexin-B, are neuropeptides with extensive projections throughout the central nervous system. They are implicated in a variety of physiological processes through their receptors, orexin type 1 (OX₁) and orexin type 2 (OX₂) receptors. Among the physiological functions of orexins, their role in sleep/wake regulation has garnered significant attention. Consequently, three orexin receptor antagonists that block both OX₁ and OX₂ receptors (dual orexin receptor antagonist; DORA) are available on the market for the treatment of insomnia. Additionally, another DORA, vornorexant, has been submitted for approval.</p><p><strong>Objective: </strong>Beyond sleep disorders, the orexin system is deeply implicated in the pathophysiology of several psychiatric disorders, including depression, anxiety, and substance use disorders.</p><p><strong>Results: </strong>Accumulating evidence indicates that orexin receptor antagonists improve behavioral abnormalities that mimic certain psychiatric disorders in animal models and are effective in treating these disorders or their symptoms in humans. Moreover, orexin receptor antagonists are expected not only to alleviate core symptoms of psychiatric disorders but also to improve sleep disturbances, which are often comorbid with these conditions.</p><p><strong>Conclusion: </strong>Drug discovery and development targeting orexin receptors should provide novel therapeutic options for the treatment of psychiatric disorders.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1669-1691"},"PeriodicalIF":3.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute nicotine vapor attenuates sensorimotor gating deficits in HIV-1 transgenic rats.","authors":"Neal A Jha, Samantha M Ayoub, M Melissa Flesher, Kathleen Morton, Megan Sikkink, Giordano de Guglielmo, Jibran Y Khokhar, Arpi Minassian, Arthur L Brody, Jared W Young","doi":"10.1007/s00213-025-06761-7","DOIUrl":"10.1007/s00213-025-06761-7","url":null,"abstract":"<p><strong>Rationale: </strong>Despite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication.</p><p><strong>Objectives: </strong>Here, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV.</p><p><strong>Methods: </strong>Male and female HIV-1Tg (n = 28) and F344 control rats (n = 29) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM).</p><p><strong>Results: </strong>Vehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV-1Tg rats, however. Nicotine vapor increased locomotor activity across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes.</p><p><strong>Conclusions: </strong>Previous findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor administration. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. Therefore, acute nicotine administration may be beneficial for attenuating sensorimotor deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1783-1796"},"PeriodicalIF":3.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-223-3p inhibits hippocampal neurons injury and exerts anti- anxiety/depression-like behaviors by directly targeting NLRP3.","authors":"Wenyuan Wang, Tingting Yang, Na Liu, Lin Yang, Cong Liu, Xiaoxiao Qi, Ning Wang, Mingwei Wang, Yanyong Wang","doi":"10.1007/s00213-025-06763-5","DOIUrl":"10.1007/s00213-025-06763-5","url":null,"abstract":"<p><p>Anxiety/depression disorders are among the most common neuropsychiatric conditions, and inflammation plays a significant role in their regulation. The involvement of miRNAs in the initiation, progression, and outcomes of anxiety disorders has been widely reported. Here, a decline in miR-223-3p expression was noticed in both IL-8-induced HT-22 cells and a rat model of anxiety/depression disorders treated with chronic unpredictable mild stress (CUMS). Our findings indicate that the overexpression of miR-223-3p significantly alleviates the effects of IL-8 on cell viability, inflammation, and oxidative stress in HT-22 cells, as verified by CCK-8 assay, ELISA assay, and flow cytometry. Through bioinformatics and luciferase reporter assays, NLRP3 was identified as a direct target of miR-223-3p. The inhibition of NLRP3 significantly reduced IL-8-induced damage to hippocampal neurons, while overexpression of NLRP3 reversed the protective effects of miR-223-3p. Moreover, increasing miR-223-3p levels significantly attenuated CUMS-induced anxiety/depression -like behaviors, such as decreased time in center in the open field test (OFT) and decreased time in open arm in the plus-maze test (EPM). The overexpression of miR-223-3p resulted in significant reductions in TNF-α, IL-1β, and SOD levels, an increase in MDA activity, as well as upregulation of cyclic adenosine monophosphate (cAMP), phosphorylated cAMP response element-binding protein (p-CREB), and brain-derived neurotrophic factor (BDNF) in the hippocampus. Overexpression of NLRP3 also reversed the effects of miR-223-3p in vivo. Thus, our research suggests that miR-223-3p can improve anxiety/depression-like behavior and inhibit hippocampal neuronal injury by targeting NLRP3, demonstrating its considerable anti-anxiety potential.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1797-1809"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pace of alcohol drinking during in natural-environment drinking is associated with heightened alcohol-related reward and negative consequences in risky drinkers.","authors":"Emily A Atkinson, Andrew M Fischer, John F Cursio, Andrea C King, Daniel J Fridberg","doi":"10.1007/s00213-025-06758-2","DOIUrl":"10.1007/s00213-025-06758-2","url":null,"abstract":"<p><strong>Background: </strong>Sensitivity to alcohol's stimulating and rewarding properties is associated with increased risk for future heavy drinking and the development and maintenance of alcohol use disorder (AUD). Further, pace of alcohol consumption varies across individuals and affects level of intoxication and subjective alcohol responses. The present study used smartphone-based high-resolution ecological momentary assessment (HR-EMA) of a heavy drinking episode in young adult risky drinkers' natural environments to examine associations between pace of drinking and subjective responses to alcohol.</p><p><strong>Method: </strong>Young adult risky drinkers (N = 248; 42% female) completed a 3-hour HR-EMA of alcohol use and subjective responses to alcohol (stimulation, sedation, feeling, liking, and wanting more) during a drinking episode in their natural environment. Analyses examined associations between drinking pace trajectories and subjective responses to alcohol, accounting for drinking context (location/presence of others) and depression.</p><p><strong>Results: </strong>Trajectory analysis revealed three drinking pace subgroups based on total drinks consumed during the 3-hour monitoring period: fast risers (~ 4 standard drinks/hour), moderate risers (~ 2.6 standard drinks/hour), and slow risers (~ 1.4 standard drinks/hour). Overall, faster pace of drinking was associated with greater alcohol stimulation and reward (liking and wanting more) and more alcohol-related negative consequences during and after the episode.</p><p><strong>Conclusions: </strong>Results further underscore the heterogeneous nature of young adult risky drinkers and suggest the possibility that these individuals may drink rapidly to experience the stimulating and rewarding effects of alcohol sooner. Resulting increases in the positive effects of alcohol may reinforce future rapid drinking behavior.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1769-1781"},"PeriodicalIF":3.5,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of muscarinic blockade on the speed of attention shifting, read-out delays and learning.","authors":"Alexander Thiele, Agnes McDonald Milner, Corwyn Hall, Lucy Mayhew, Anthony Carter, Sidharth Sanjeev","doi":"10.1007/s00213-025-06757-3","DOIUrl":"10.1007/s00213-025-06757-3","url":null,"abstract":"<p><p>The study aimed to investigate to what extent blockade of muscarinic receptors affects the speed of endogenous versus exogenous attentional shift times, and how it affects learning of attention shifting, cue detection and signal readout. Subjects viewed an array of 10 moving clocks and reported the time a clock indicated when cued. Target clocks were indicated by peripheral or central cues, including conditions of pre-cuing. For peripheral and central cuing, it yielded a compound measure of how long it took to detect the cue, shift attention to the relevant clock and read the time on the clock. For the pre-cue condition it yielded a measure of how long it took to detect the cue and read the time on the clock when attention could have been pre-allocated to the target clock. In study 1, each subject participated in 2 sessions (scopolamine/placebo), whereby the order of drug intake was counterbalanced across subjects, and subjects were blinded to conditions. Scopolamine/placebo was administered before a psychophysical experiment was conducted. In study 2, the effect of muscarinic blockade on learning induced improvements of cue detection, attention shift times (for exogenous and endogenous conditions), and signal readout was investigated. Here scopolamine/placebo was administered immediately after the first (of two) psychophysical sessions, whereby a given subject either received scopolamine or placebo pills. Confirming previous results, we show that pre-cuing resulted in the shortest read-out delays, followed by exogenous cuing, with endogenous read-out delays being slowest. Scopolamine application increased readout-delays in a dose dependent manner. This was mainly driven by increased readout-delays for pre-cue conditions, and to some extent for exogenous cue conditions. It suggests that muscarinic blockade affected the ability to pre-allocated attention to a cued location, as well as to react to peripheral cues. Additionally, blockade of muscarinic receptors immediately after the first session reduced learning dependent improvement of read-out delays. These results demonstrate that muscarinic receptors play an important in detecting cues, and fast read-out of cued information, and they contribute to the learning thereof.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":"1757-1768"},"PeriodicalIF":3.3,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}