Scopolamine disrupts place navigation in rats and humans: a translational validation of the Hidden Goal Task in the Morris water maze and a real maze for humans

Laczó, Jan; Marková, Hana; Lobellová, Veronika; Gažová, Ivana; Pařízková, Martina; Cerman, Jiří; Nekovarova, Tereza; Valeš, Karel; Klovrzová, Sylva; Harrison, John; Windisch, Manfred; Vlček, Kamil; Svoboda, Jan; Hort, Jakub; Stuchlı́k, Aleš

doi:10.1007/s00213-016-4488-2

Cited by 28 publications

(21 citation statements)

References 58 publications

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“…The authors reported successful validation of the tasks and scopolamine, as no significant differences were found between the human volunteers and the animals. Donepezil was shown to exhibit some ameliorative effect; however, this was not clear in all cases ( 80 ).…”

Section: Antimuscarinic Agents In Spatial Tasksmentioning

confidence: 96%

“…Scopolamine-induced cognitive impairment has also been shown to possess good validity as a translational model in research. Laczó et al ( 80 ) compared the effects of scopolamine administration (as well as its coadministration with donepezil, an AChE inhibitor) in rats and humans in the MWM and the Hidden Goal Task, an analog of the water maze fit for use in humans. The authors reported successful validation of the tasks and scopolamine, as no significant differences were found between the human volunteers and the animals.…”

Section: Antimuscarinic Agents In Spatial Tasksmentioning

confidence: 99%

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Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation

2017

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Muscarinic acetylcholine receptors (mAChRs) have been found to regulate many diverse functions, ranging from motivation and feeding to spatial navigation, an important and widely studied type of cognitive behavior. Systemic administration of non-selective antagonists of mAChRs, such as scopolamine or atropine, have been found to have adverse effects on a vast majority of place navigation tasks. However, many of these results may be potentially confounded by disruptions of functions other than spatial learning and memory. Although studies with selective antimuscarinics point to mutually opposite effects of M1 and M2 receptors, their particular contribution to spatial cognition is still poorly understood, partly due to a lack of truly selective agents. Furthermore, constitutive knock-outs do not always support results from selective antagonists. For modeling impaired spatial cognition, the scopolamine-induced amnesia model still maintains some limited validity, but there is an apparent need for more targeted approaches such as local intracerebral administration of antagonists, as well as novel techniques such as optogenetics focused on cholinergic neurons and chemogenetics aimed at cells expressing metabotropic mAChRs.

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Section: Antimuscarinic Agents In Spatial Tasksmentioning

confidence: 96%

Section: Antimuscarinic Agents In Spatial Tasksmentioning

confidence: 99%

Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation

2017

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“…A 3-month openlabel study has shown that a computerized human analogue of the Morris water maze has the potential to measure the effects of donepezil in mild AD 145 . Subsequent research has shown that the disruptive effect of scopolamine on place navigation can be reverted by donepezil, a finding that was demonstrated using both rodent and human versions of the Morris water maze 146 .…”

Section: [H1] Conclusionmentioning

confidence: 98%

Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

et al. 2018

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Detection of incipient Alzheimer disease (AD) pathophysiology is critical to identify preclinical individuals and target potentially disease-modifying therapies towards them. Current neuroimaging and biomarker research is strongly focused in this direction, with the aim of establishing AD fingerprints to identify individuals at high risk of developing this disease. By contrast, cognitive fingerprints for incipient AD are virtually non-existent as diagnostics and outcomes measures are still focused on episodic memory deficits as the gold standard for AD, despite their low sensitivity and specificity for identifying at-risk individuals. This Review highlights a novel feature of cognitive evaluation for incipient AD by focusing on spatial navigation and orientation deficits, which are increasingly shown to be present in at-risk individuals. Importantly, the navigation system in the brain overlaps substantially with the regions affected by AD in both animal models and humans. Notably, spatial navigation has fewer verbal, cultural and educational biases than current cognitive tests and could enable a more uniform, global approach towards cognitive fingerprints of AD and better cognitive treatment outcome measures in future multicentre trials. The current Review appraises the available evidence for spatial navigation and/or orientation deficits in preclinical, prodromal and confirmed AD and identifies research gaps and future research priorities.

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“…While at T1, a paper version of the supermarket map was used to record responses, an alternative form of the VST was employed 18 months later at T2, to facilitate electronic and automatic recording of participant responses on a 9.7inch iPad. VST trials (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) in both versions were identical. At T2, the scoring parameter for VST allocentric memory was updated to include the exact distance of error (here referred to as map drop error), with the specific aim of increasing the sensitivity of the VST sub-measure to measure spatial memory impairment.…”

Section: Methodsmentioning

confidence: 93%

“…Spatial navigation shows promise as an outcome measure for preclinical Alzheimer disease (AD) in drug treatment trials, but it's test-retest reliability is not clear [1][2][3][4]. Drug development for AD has been plagued by the failure of cognitive outcomes measures to detect treatment response due to i) insufficient sensitivity and specificity for preclinical neuropathology and/or ii) poor test-retest reliability, both of which can mask neural response to treatment [5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Test-retest reliability of spatial navigation in adults at-risk of Alzheimer’s disease

et al. 2020

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The Virtual Supermarket Task (VST) and Sea Hero Quest detect high-genetic-risk Alzheimer's disease (AD). We aimed to determine their test-retest reliability in a preclinical AD population. Over two time points, separated by an 18-month period, 59 cognitively healthy individuals underwent a neuropsychological and spatial navigation assessment. At baseline, participants were classified as low-genetic-risk of AD or high-genetic-risk of AD. We calculated two-way mixed effects intraclass correlation coefficients (ICC) for task parameters and used repeated measures ANOVAS to determine whether genetic risk or sex contributed to test-retest variability. The egocentric parameter of the VST measure showed the highest test-retest reliability (ICC = .72), followed by the SHQ distance travelled parameter (ICC = .50). Post hoc longitudinal analysis showed that boundary-based navigation predicts worsening episodic memory concerns in high-risk (F = 5.01, P = 0.03), but in not low-risk, AD candidates. The VST and the Sea Hero Quest produced parameters with acceptable testretest reliability. Further research in larger sample sizes is desirable.

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Scopolamine disrupts place navigation in rats and humans: a translational validation of the Hidden Goal Task in the Morris water maze and a real maze for humans

Cited by 28 publications

References 58 publications

Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation

Drugs Interfering with Muscarinic Acetylcholine Receptors and Their Effects on Place Navigation

Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Test-retest reliability of spatial navigation in adults at-risk of Alzheimer’s disease

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