Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat.
Saved in:
| Title: | Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat. |
|---|---|
| Authors: | Woolley, M., Waters, K., Gartlon, J., Lacroix, L., Jennings, C., Shaughnessy, F., Ong, A., Pemberton, D., Harries, M., Southam, E., Jones, D., Dawson, L. |
| Source: | Psychopharmacology. Jan2009, Vol. 202 Issue 1-3, p343-354. 12p. 2 Charts, 6 Graphs. |
| Subjects: | Laboratory rats, Hippocampus (Brain), Cerebral cortex, Cognition research, Frontal lobe, Prefrontal cortex, Neurotransmitters |
| Abstract: | Positive allosteric modulators of the glutamatergic α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor do not stimulate AMPA receptors directly but delay deactivation of the receptor and/or slow its desensitisation. This results in increased synaptic responses and enhanced long-term potentiation. Thus, it has been suggested that such compounds may have utility for the treatment of cognitive impairment. The objective of the study was to investigate the effect of an AMPA positive modulator, CX691, (1) in three rodent models of learning and memory, (2) on neurochemistry in the dorsal hippocampus and medial prefrontal cortex following acute administration, and (3) on brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the rat hippocampus following acute and sub-chronic administration. CX691 attenuated a scopolamine-induced impairment of cued fear conditioning following acute administration (0.1 mg/kg p.o.) and a temporally induced deficit in novel object recognition following both acute (0.1 and 1.0 mg/kg p.o.) and sub-chronic (bi-daily for 7 days) administration (0.01, 0.03, 0.1 mg/kg p.o.). It also improved attentional set-shifting following sub-chronic administration (0.3 mg/kg p.o.). Acute CX691 (0.1, 0.3 and 1.0 mg/kg, p.o.) increased extracellular levels of acetylcholine in the dorsal hippocampus and medial prefrontal cortex and dopamine in the medial prefrontal cortex. Sub-chronic administration of CX691 (0.1 mg/kg, p.o.) elevated BDNF mRNA expression in both the whole and CA1 sub-region of the hippocampus ( P < 0.05). Collectively, these data support the pro-cognitive activity reported for AMPA receptor positive modulators and suggest that these compounds may be of benefit in treating disorders characterised by cognitive deficits such as Alzheimer’s disease and schizophrenia. [ABSTRACT FROM AUTHOR] |
| Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
|---|---|
| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 36327178 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Woolley%2C+M%2E%22">Woolley, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Waters%2C+K%2E%22">Waters, K.</searchLink><br /><searchLink fieldCode="AR" term="%22Gartlon%2C+J%2E%22">Gartlon, J.</searchLink><br /><searchLink fieldCode="AR" term="%22Lacroix%2C+L%2E%22">Lacroix, L.</searchLink><br /><searchLink fieldCode="AR" term="%22Jennings%2C+C%2E%22">Jennings, C.</searchLink><br /><searchLink fieldCode="AR" term="%22Shaughnessy%2C+F%2E%22">Shaughnessy, F.</searchLink><br /><searchLink fieldCode="AR" term="%22Ong%2C+A%2E%22">Ong, A.</searchLink><br /><searchLink fieldCode="AR" term="%22Pemberton%2C+D%2E%22">Pemberton, D.</searchLink><br /><searchLink fieldCode="AR" term="%22Harries%2C+M%2E%22">Harries, M.</searchLink><br /><searchLink fieldCode="AR" term="%22Southam%2C+E%2E%22">Southam, E.</searchLink><br /><searchLink fieldCode="AR" term="%22Jones%2C+D%2E%22">Jones, D.</searchLink><br /><searchLink fieldCode="AR" term="%22Dawson%2C+L%2E%22">Dawson, L.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Jan2009, Vol. 202 Issue 1-3, p343-354. 12p. 2 Charts, 6 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Laboratory+rats%22">Laboratory rats</searchLink><br /><searchLink fieldCode="DE" term="%22Hippocampus+%28Brain%29%22">Hippocampus (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22Cerebral+cortex%22">Cerebral cortex</searchLink><br /><searchLink fieldCode="DE" term="%22Cognition+research%22">Cognition research</searchLink><br /><searchLink fieldCode="DE" term="%22Frontal+lobe%22">Frontal lobe</searchLink><br /><searchLink fieldCode="DE" term="%22Prefrontal+cortex%22">Prefrontal cortex</searchLink><br /><searchLink fieldCode="DE" term="%22Neurotransmitters%22">Neurotransmitters</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Positive allosteric modulators of the glutamatergic α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptor do not stimulate AMPA receptors directly but delay deactivation of the receptor and/or slow its desensitisation. This results in increased synaptic responses and enhanced long-term potentiation. Thus, it has been suggested that such compounds may have utility for the treatment of cognitive impairment. The objective of the study was to investigate the effect of an AMPA positive modulator, CX691, (1) in three rodent models of learning and memory, (2) on neurochemistry in the dorsal hippocampus and medial prefrontal cortex following acute administration, and (3) on brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) expression in the rat hippocampus following acute and sub-chronic administration. CX691 attenuated a scopolamine-induced impairment of cued fear conditioning following acute administration (0.1 mg/kg p.o.) and a temporally induced deficit in novel object recognition following both acute (0.1 and 1.0 mg/kg p.o.) and sub-chronic (bi-daily for 7 days) administration (0.01, 0.03, 0.1 mg/kg p.o.). It also improved attentional set-shifting following sub-chronic administration (0.3 mg/kg p.o.). Acute CX691 (0.1, 0.3 and 1.0 mg/kg, p.o.) increased extracellular levels of acetylcholine in the dorsal hippocampus and medial prefrontal cortex and dopamine in the medial prefrontal cortex. Sub-chronic administration of CX691 (0.1 mg/kg, p.o.) elevated BDNF mRNA expression in both the whole and CA1 sub-region of the hippocampus ( P < 0.05). Collectively, these data support the pro-cognitive activity reported for AMPA receptor positive modulators and suggest that these compounds may be of benefit in treating disorders characterised by cognitive deficits such as Alzheimer’s disease and schizophrenia. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=36327178 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s00213-008-1325-2 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 343 Subjects: – SubjectFull: Laboratory rats Type: general – SubjectFull: Hippocampus (Brain) Type: general – SubjectFull: Cerebral cortex Type: general – SubjectFull: Cognition research Type: general – SubjectFull: Frontal lobe Type: general – SubjectFull: Prefrontal cortex Type: general – SubjectFull: Neurotransmitters Type: general Titles: – TitleFull: Evaluation of the pro-cognitive effects of the AMPA receptor positive modulator, 5-(1-piperidinylcarbonyl)-2,1,3-benzoxadiazole (CX691), in the rat. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Woolley, M. – PersonEntity: Name: NameFull: Waters, K. – PersonEntity: Name: NameFull: Gartlon, J. – PersonEntity: Name: NameFull: Lacroix, L. – PersonEntity: Name: NameFull: Jennings, C. – PersonEntity: Name: NameFull: Shaughnessy, F. – PersonEntity: Name: NameFull: Ong, A. – PersonEntity: Name: NameFull: Pemberton, D. – PersonEntity: Name: NameFull: Harries, M. – PersonEntity: Name: NameFull: Southam, E. – PersonEntity: Name: NameFull: Jones, D. – PersonEntity: Name: NameFull: Dawson, L. IsPartOfRelationships: – BibEntity: Dates: – D: 15 M: 01 Text: Jan2009 Type: published Y: 2009 Identifiers: – Type: issn-print Value: 00333158 Numbering: – Type: volume Value: 202 – Type: issue Value: 1-3 Titles: – TitleFull: Psychopharmacology Type: main |
| ResultId | 1 |
