Modulation of MK-801-induced behaviour by noradrenergic agents in mice.
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| Title: | Modulation of MK-801-induced behaviour by noradrenergic agents in mice. |
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| Authors: | Harkin, Andrew, Morris, Kathleen, Kelly, John P., O'Donnell, James M., Leonard, Brian E. |
| Source: | Psychopharmacology. 2001, Vol. 154 Issue 2, p177. 12p. 1 Chart, 8 Graphs. |
| Subjects: | Noradrenaline, Methyl aspartate, Mice, Physiology, Chemicals |
| Abstract: | Abstract Rationale: Inhibition of glutamatergic N-methyl-D-aspartate (NMDA) receptors following the administration of NMDA receptor antagonists results in psychotic-like behaviour. Whereas it is known that pharmacological manipulation of dopaminergic and serotonergic pathways affect this drug-induced psychosis, a role for noradrenaline has not yet been clearly defined. Objectives: Thus, in the present study, we assessed a possible role for noradrenaline in the behavioural response to the non-competitive NMDA receptor anatgonist, MK-801, in male CD-I mice. Results: MK-801 (0.02-1.28 mg/kg; ED[sub 50] 0.2 mg/kg; S.C.) induced a dose-dependent increase in locomotor, stereotypic and ataxic behaviours. Pre-treatment with the noradrenaline re-uptake inhibitors, desipramine (10 mg/kg; i.p.) and reboxetine (20 mg/kg; i.p.), attenuated the locomotor, stereotypic and ataxic response to MK-801 (0.2 mg/kg; S.C.). The noradrenergic system was lesioned with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, 50 mg/kg; i.p., 7 and 4 days prior to challenge) to reduce noradrenaline concentrations in the cortex by 70%-80%. Whereas DSP-4 lesioning had little effect on the response to MK-801, it completely reversed the attenuating effects of reboxetine. Pre-treatment with the alpha[sub 2] adrenoceptor agonist, clonidine (0.2 mg/kg; i.p.), and the antagonist, yohimbine (2 mg/kg; i.p.), attenuated and potentiated the response to MK-801, respectively. Pre-treatment with the alpha[sub 1] adrenoceptor antagonist, prazosin (2 mg/kg; i.p.), reduced the MK-801-induced response. Conclusions: It therefore appears that presynaptic noradrenergic alpha[sub 2] and postsynaptic alpha[sub 1] adrenoceptor stimulation exert opposing effects on the behavioural expression of MK-801 in mice. [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 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 4693282 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Modulation of MK-801-induced behaviour by noradrenergic agents in mice. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Harkin%2C+Andrew%22">Harkin, Andrew</searchLink><br /><searchLink fieldCode="AR" term="%22Morris%2C+Kathleen%22">Morris, Kathleen</searchLink><br /><searchLink fieldCode="AR" term="%22Kelly%2C+John+P%2E%22">Kelly, John P.</searchLink><br /><searchLink fieldCode="AR" term="%22O'Donnell%2C+James+M%2E%22">O'Donnell, James M.</searchLink><br /><searchLink fieldCode="AR" term="%22Leonard%2C+Brian+E%2E%22">Leonard, Brian E.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. 2001, Vol. 154 Issue 2, p177. 12p. 1 Chart, 8 Graphs. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Noradrenaline%22">Noradrenaline</searchLink><br /><searchLink fieldCode="DE" term="%22Methyl+aspartate%22">Methyl aspartate</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink><br /><searchLink fieldCode="DE" term="%22Physiology%22">Physiology</searchLink><br /><searchLink fieldCode="DE" term="%22Chemicals%22">Chemicals</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Abstract Rationale: Inhibition of glutamatergic N-methyl-D-aspartate (NMDA) receptors following the administration of NMDA receptor antagonists results in psychotic-like behaviour. Whereas it is known that pharmacological manipulation of dopaminergic and serotonergic pathways affect this drug-induced psychosis, a role for noradrenaline has not yet been clearly defined. Objectives: Thus, in the present study, we assessed a possible role for noradrenaline in the behavioural response to the non-competitive NMDA receptor anatgonist, MK-801, in male CD-I mice. Results: MK-801 (0.02-1.28 mg/kg; ED[sub 50] 0.2 mg/kg; S.C.) induced a dose-dependent increase in locomotor, stereotypic and ataxic behaviours. Pre-treatment with the noradrenaline re-uptake inhibitors, desipramine (10 mg/kg; i.p.) and reboxetine (20 mg/kg; i.p.), attenuated the locomotor, stereotypic and ataxic response to MK-801 (0.2 mg/kg; S.C.). The noradrenergic system was lesioned with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride (DSP-4, 50 mg/kg; i.p., 7 and 4 days prior to challenge) to reduce noradrenaline concentrations in the cortex by 70%-80%. Whereas DSP-4 lesioning had little effect on the response to MK-801, it completely reversed the attenuating effects of reboxetine. Pre-treatment with the alpha[sub 2] adrenoceptor agonist, clonidine (0.2 mg/kg; i.p.), and the antagonist, yohimbine (2 mg/kg; i.p.), attenuated and potentiated the response to MK-801, respectively. Pre-treatment with the alpha[sub 1] adrenoceptor antagonist, prazosin (2 mg/kg; i.p.), reduced the MK-801-induced response. Conclusions: It therefore appears that presynaptic noradrenergic alpha[sub 2] and postsynaptic alpha[sub 1] adrenoceptor stimulation exert opposing effects on the behavioural expression of MK-801 in mice. [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.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s002130000630 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 177 Subjects: – SubjectFull: Noradrenaline Type: general – SubjectFull: Methyl aspartate Type: general – SubjectFull: Mice Type: general – SubjectFull: Physiology Type: general – SubjectFull: Chemicals Type: general Titles: – TitleFull: Modulation of MK-801-induced behaviour by noradrenergic agents in mice. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Harkin, Andrew – PersonEntity: Name: NameFull: Morris, Kathleen – PersonEntity: Name: NameFull: Kelly, John P. – PersonEntity: Name: NameFull: O'Donnell, James M. – PersonEntity: Name: NameFull: Leonard, Brian E. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: 2001 Type: published Y: 2001 Identifiers: – Type: issn-print Value: 00333158 Numbering: – Type: volume Value: 154 – Type: issue Value: 2 Titles: – TitleFull: Psychopharmacology Type: main |
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