Effect of muscarinic blockade on the speed of attention shifting, read-out delays and learning.

IF 3.5 3区 医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2025-02-15 DOI:10.1007/s00213-025-06757-3
Alexander Thiele, Agnes McDonald Milner, Corwyn Hall, Lucy Mayhew, Anthony Carter, Sidharth Sanjeev
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Abstract

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.

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来源期刊
Psychopharmacology
Psychopharmacology 医学-精神病学
CiteScore
7.10
自引率
5.90%
发文量
257
审稿时长
2-4 weeks
期刊介绍: Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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