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
Language English Country Germany Media print-electronic
Document type Journal Article, Randomized Controlled Trial
PubMed
27885411
DOI
10.1007/s00213-016-4488-2
PII: 10.1007/s00213-016-4488-2
Knihovny.cz E-resources
- Keywords
- Acetylcholinesterase inhibitor *, Human *, Rat *, Scopolamine *, Spatial orientation *,
- MeSH
- Muscarinic Antagonists pharmacology MeSH
- Maze Learning drug effects MeSH
- Cholinesterase Inhibitors pharmacology MeSH
- Donepezil MeSH
- Adult MeSH
- Double-Blind Method MeSH
- Indans pharmacology MeSH
- Rats MeSH
- Humans MeSH
- Young Adult MeSH
- Piperidines pharmacology MeSH
- Rats, Wistar MeSH
- Spatial Navigation drug effects MeSH
- Scopolamine pharmacology MeSH
- Animals MeSH
- Check Tag
- Adult MeSH
- Rats MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Muscarinic Antagonists MeSH
- Cholinesterase Inhibitors MeSH
- Donepezil MeSH
- Indans MeSH
- Piperidines MeSH
- Scopolamine MeSH
RATIONALE: Development of new drugs for treatment of Alzheimer's disease (AD) requires valid paradigms for testing their efficacy and sensitive tests validated in translational research. OBJECTIVES: We present validation of a place-navigation task, a Hidden Goal Task (HGT) based on the Morris water maze (MWM), in comparable animal and human protocols. METHODS: We used scopolamine to model cognitive dysfunction similar to that seen in AD and donepezil, a symptomatic medication for AD, to assess its potential reversible effect on this scopolamine-induced cognitive dysfunction. We tested the effects of scopolamine and the combination of scopolamine and donepezil on place navigation and compared their effects in human and rat versions of the HGT. Place navigation testing consisted of 4 sessions of HGT performed at baseline, 2, 4, and 8 h after dosing in humans or 1, 2.5, and 5 h in rats. RESULTS: Scopolamine worsened performance in both animals and humans. In the animal experiment, co-administration of donepezil alleviated the negative effect of scopolamine. In the human experiment, subjects co-administered with scopolamine and donepezil performed similarly to subjects on placebo and scopolamine, indicating a partial ameliorative effect of donepezil. CONCLUSIONS: In the task based on the MWM, scopolamine impaired place navigation, while co-administration of donepezil alleviated this effect in comparable animal and human protocols. Using scopolamine and donepezil to challenge place navigation testing can be studied concurrently in animals and humans and may be a valid and reliable model for translational research, as well as for preclinical and clinical phases of drug trials.
Imperial College Faculty of Medicine South Kensington Campus London SW7 2AZ UK
Metis Cognition Ltd Park House Kilmington Common Warminster Wiltshire BA12 6QY UK
National Institute of Mental Health Topolova 748 250 67 Klecany Czech Republic
NeuroScios GmbH Willersdorferstrasse 6 A 8061 Radegund Graz Austria
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