Yes / Cholinergic dysfunction has been shown to be central to the pathophysiology of Alzheimer’s disease and
has also been postulated to contribute to cognitive dysfunction observed in various psychiatric disorders,
including schizophrenia. Deficits are found across a number of cognitive domains and in spite of several
attempts to develop new therapies, these remain an unmet clinical need.
In the current study we investigated the efficacy of donepezil, risperidone and selective nicotinic α7
and α4β2 receptor agonists to reverse a delay-induced deficit in recognition memory. Adult female
Hooded Lister rats received drug treatments and were tested in the novel object recognition (NOR) task
following a 6 h inter-trial interval (ITI). In all treatment groups, there was no preference for the left or
right identical objects in the acquisition trial. Risperidone failed to enhance recognition memory in this
paradigm whereas donepezil was effective such that rats discriminated between the novel and familiar
object in the retention trial following a 6 h ITI. Although a narrow dose range of PNU-282987 and RJR-
2403 was tested, only one dose of each increased recognition memory, the highest dose of PNU-282987
(10 mg/kg) and the lowest dose of RJR-2403 (0.1 mg/kg), indicative of enhanced cognitive performance.
Interestingly, these compounds were also efficacious when administered either before the acquisition
or the retention trial of the task, suggesting an important role for nicotinic receptor subtypes in the
formation and retrieval of recognition memory. / This work was conducted at the University of Bradford and was funded by b-neuro. However all our recent studies mentioned in the discussion section have been conducted at the University of Manchester (UoM), and funded by b-neuro, Autifony, Innovate UK (formerly TSB) and UoM
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/8460 |
| Date | 2015 August 1930 |
| Creators | McLean, Samantha L., Grayson, Ben, Marsh, S., Zarroug, S.H.O., Harte, Michael K., Neill, Joanna C. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted manuscript |
| Rights | © 2016 Elsevier. Reproduced in accordance with the publisher's self-archiving policy. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/, CC-BY-NC-ND |
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