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{
    "pk": 5289,
    "title": "Cognitive Deficits in the R6/2 model of Huntington’s Disease and Amelioration with Donepezil",
    "subtitle": null,
    "abstract": "The neurodegenerative disorder Huntington’s disease (HD) is characterized by motor dysfunction, cognitive impairment and psychiatric symptoms. The R6/2 (120 CAG repeats) mouse model of HD recapitulates many of the symptoms of the disease, including marked impairments in cognition and severe motor deficits. As cholinergic function has been reported to be affected in both HD patients and this mouse model, we tested whether treatment with the cholinesterase inhibitor donepezil could improve the R6/2 mice performance in the two-choice swim tank visual discrimination and reversal task. In this test mice are trained to swim towards a light cued platform located on one side of a water-filled tank. Once mice reach an acquisition criterion a reversal ensues. Wild-type and R6/2 mice were dosed with donepezil (0.6 mg/kg/day) or vehicle starting at 8 weeks of age and tested starting at 9 weeks of age. In experiment 1, vehicle-treated R6/2 mice showed a significant deficit during acquisition and reversal as compared to vehicle-treated WT mice. Donepezil improved reversal in the R6/2 group. In experiment 2, we confirmed the beneficial effect of donepezil on reversal in similar conditions. Donepezil had no effect on activity as measured in the open field test or through the latency to reach the platform during the swim test. We suggest that the donepezil-induced improvements in cognitive function observed in the R6/2 transgenic model of HD may reflect amelioration of deficits in cholinergic function that have been reported previously in this model. Further work is required to confirm the findings of these interesting although preliminary studies.",
    "language": "en",
    "license": {
        "name": "Creative Commons Attribution 4.0",
        "short_name": "CC BY 4.0",
        "text": "Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.\r\n\r\nNo additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.",
        "url": "https://creativecommons.org/licenses/by/4.0"
    },
    "keywords": [
        {
            "word": "cognition"
        },
        {
            "word": "cognitive deficit"
        },
        {
            "word": "International Journal of Comparative Psychology"
        },
        {
            "word": "animal model"
        },
        {
            "word": "R6/2"
        },
        {
            "word": "Huntington Disease"
        },
        {
            "word": "Donepezil"
        }
    ],
    "section": "Research Article",
    "is_remote": true,
    "remote_url": "https://escholarship.org/uc/item/7ck5k465",
    "frozenauthors": [
        {
            "first_name": "Carol",
            "middle_name": "A.",
            "last_name": "Murphy",
            "name_suffix": "",
            "institution": "PsychoGenics, New York, NY",
            "department": "None"
        },
        {
            "first_name": "Neil",
            "middle_name": "E.",
            "last_name": "Paterson",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Angela",
            "middle_name": "",
            "last_name": "Chen",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Washington",
            "middle_name": "",
            "last_name": "Arias",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Dansha",
            "middle_name": "",
            "last_name": "He",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "William",
            "middle_name": "",
            "last_name": "Alosio",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Steven",
            "middle_name": "",
            "last_name": "Oakeshott",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Andrew",
            "middle_name": "",
            "last_name": "Farrar",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Liliana",
            "middle_name": "",
            "last_name": "Menalled",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Sylvie",
            "middle_name": "",
            "last_name": "Ramboz",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY",
            "department": "None"
        },
        {
            "first_name": "Dani",
            "middle_name": "",
            "last_name": "Brunner",
            "name_suffix": "",
            "institution": "PsychoGenics, Tarrytown, NY\nColumbia University, New York, NY",
            "department": "None"
        },
        {
            "first_name": "David",
            "middle_name": "",
            "last_name": "Howland",
            "name_suffix": "",
            "institution": "CHDI Management/CHDI Foundation, Princeton, NJ",
            "department": "None"
        },
        {
            "first_name": "Larry",
            "middle_name": "C.",
            "last_name": "Park",
            "name_suffix": "",
            "institution": "CHDI Management/CHDI Foundation, Princeton, NJ",
            "department": "None"
        }
    ],
    "date_submitted": "2014-01-06T22:24:12Z",
    "date_accepted": "2014-01-06T22:24:12Z",
    "date_published": "2014-07-06T07:00:00Z",
    "render_galley": null,
    "galleys": [
        {
            "label": "",
            "type": "",
            "path": "https://journalpub.escholarship.org/uclapsych_ijcp/article/5289/galley/3163/download/"
        }
    ]
}