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Nicotinic ?7 and ?4?2 agonists enhance the formation and retrieval of recognition memory: potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders

Nicotinic ?7 and ?4?2 agonists enhance the formation and retrieval of recognition memory: potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders
Nicotinic ?7 and ?4?2 agonists enhance the formation and retrieval of recognition memory: potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders
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 ?7 and ?4?2 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 hour 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 hr 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.
object recognition memory, female rat, delay-dependent deficits, &alpha, 7 nicotinic receptors, 4&beta, 2 nicotinic receptors
0166-4328
1-38
McLean, Samantha L.
9249064f-d5db-4fbd-8baf-46915baa7b4f
Grayson, Ben
3c8b3cdc-04c0-45a6-bc9e-88dc3ea1e6e9
Marsh, Samuel
1f872274-caa8-4cb7-96c1-4755af19186e
Zarroug, Samah H.O.
83c45180-0967-4957-a618-7dc666ac4b7d
Harte, Michael K.
fa3e17fe-55bb-4401-a2ab-2fd1fc4a06de
Neill, Jo C.
7dfcd57e-da8e-480b-8649-9941967ca9a6
McLean, Samantha L.
9249064f-d5db-4fbd-8baf-46915baa7b4f
Grayson, Ben
3c8b3cdc-04c0-45a6-bc9e-88dc3ea1e6e9
Marsh, Samuel
1f872274-caa8-4cb7-96c1-4755af19186e
Zarroug, Samah H.O.
83c45180-0967-4957-a618-7dc666ac4b7d
Harte, Michael K.
fa3e17fe-55bb-4401-a2ab-2fd1fc4a06de
Neill, Jo C.
7dfcd57e-da8e-480b-8649-9941967ca9a6

McLean, Samantha L., Grayson, Ben, Marsh, Samuel, Zarroug, Samah H.O., Harte, Michael K. and Neill, Jo C. (2015) Nicotinic ?7 and ?4?2 agonists enhance the formation and retrieval of recognition memory: potential mechanisms for cognitive performance enhancement in neurological and psychiatric disorders. Behavioural Brain Research, 1-38. (doi:10.1016/j.bbr.2015.08.037). (PMID:26327238)

Record type: Article

Abstract

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 ?7 and ?4?2 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 hour 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 hr 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.

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Accepted/In Press date: 27 August 2015
e-pub ahead of print date: 30 August 2015
Keywords: object recognition memory, female rat, delay-dependent deficits, &alpha, 7 nicotinic receptors, 4&beta, 2 nicotinic receptors
Organisations: Psychology

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Local EPrints ID: 383086
URI: http://eprints.soton.ac.uk/id/eprint/383086
ISSN: 0166-4328
PURE UUID: 2f0e9f4c-e273-4c97-b8cb-58b3d3023e12

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Date deposited: 22 Oct 2015 13:33
Last modified: 14 Mar 2024 21:39

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Contributors

Author: Samantha L. McLean
Author: Ben Grayson
Author: Samuel Marsh
Author: Samah H.O. Zarroug
Author: Michael K. Harte
Author: Jo C. Neill

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