Metyrapone displays antidepressant-like properties in preclinical paradigms.
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| Title: | Metyrapone displays antidepressant-like properties in preclinical paradigms. |
|---|---|
| Authors: | Healy, David G., Harkin, Andrew, Cryan, John F., Kelly, John P., Leonard, B. E. |
| Source: | Psychopharmacology. 1999, Vol. 145 Issue 3, p303. 6p. |
| Subjects: | Glucocorticoids, Mental depression, Antidepressants, Therapeutics |
| Abstract: | Abstract A possible involvement of glucocorticoids in the aetiology of depression is suggested by commonly reported hypothalamo-pituitary-adrenocortical (HPA) axis abnormalities in depressed patients, the modulation of the HPA axis by antidepressant drugs and clinical reports of antidepressant efficacy with antiglucocorticoid agents. The effects of treatment with metyrapone, a glucocorticoid synthesis inhibitor, and the tricyclic antidepressant, desipramine, in two rodent models of depression, namely the forced swim test and olfactory bulbectomized (OB) rat, were investigated. In addition, the effect of chronic metyrapone and desipramine treatments on the hypothermic response to a challenge with the 5-HT[sub 1A] agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was assessed. There is experimental evidence to suggest that attenuation of the hypothermic response to this agonist occurs following chronic antidepressant treatment. In the forced swim test, metyrapone (50 mg/kg) and desipramine (10 mg/kg) significantly reduced the immobility time. In the olfactory bulbectomized rat model of depression, chronic administration (14 days) of metyrapone (50 mg/kg b.i.d.) and desipramine (5 mg/kg b.i.d.) attenuated the OB-related hyperactivity in a novel stressful environment. Chronic metyrapone treatment (50 mg/kg b.i.d.) attenuated the hypothermic response to an acute challenge with 8-OH-DPAT (0.05 mg/kg SC), indicating a change to the sensitivity of 5-HT[sub 1A] receptors. These preclinical tests demonstrate an antidepressant-like profile for metyrapone. Further exploration of the therapeutic potential and possible mechanism of action of glucocorticoid antagonism in depression is warranted. [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: 4694169 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Metyrapone displays antidepressant-like properties in preclinical paradigms. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Healy%2C+David+G%2E%22">Healy, David G.</searchLink><br /><searchLink fieldCode="AR" term="%22Harkin%2C+Andrew%22">Harkin, Andrew</searchLink><br /><searchLink fieldCode="AR" term="%22Cryan%2C+John+F%2E%22">Cryan, John F.</searchLink><br /><searchLink fieldCode="AR" term="%22Kelly%2C+John+P%2E%22">Kelly, John P.</searchLink><br /><searchLink fieldCode="AR" term="%22Leonard%2C+B%2E+E%2E%22">Leonard, B. E.</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. 1999, Vol. 145 Issue 3, p303. 6p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Glucocorticoids%22">Glucocorticoids</searchLink><br /><searchLink fieldCode="DE" term="%22Mental+depression%22">Mental depression</searchLink><br /><searchLink fieldCode="DE" term="%22Antidepressants%22">Antidepressants</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Abstract A possible involvement of glucocorticoids in the aetiology of depression is suggested by commonly reported hypothalamo-pituitary-adrenocortical (HPA) axis abnormalities in depressed patients, the modulation of the HPA axis by antidepressant drugs and clinical reports of antidepressant efficacy with antiglucocorticoid agents. The effects of treatment with metyrapone, a glucocorticoid synthesis inhibitor, and the tricyclic antidepressant, desipramine, in two rodent models of depression, namely the forced swim test and olfactory bulbectomized (OB) rat, were investigated. In addition, the effect of chronic metyrapone and desipramine treatments on the hypothermic response to a challenge with the 5-HT[sub 1A] agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) was assessed. There is experimental evidence to suggest that attenuation of the hypothermic response to this agonist occurs following chronic antidepressant treatment. In the forced swim test, metyrapone (50 mg/kg) and desipramine (10 mg/kg) significantly reduced the immobility time. In the olfactory bulbectomized rat model of depression, chronic administration (14 days) of metyrapone (50 mg/kg b.i.d.) and desipramine (5 mg/kg b.i.d.) attenuated the OB-related hyperactivity in a novel stressful environment. Chronic metyrapone treatment (50 mg/kg b.i.d.) attenuated the hypothermic response to an acute challenge with 8-OH-DPAT (0.05 mg/kg SC), indicating a change to the sensitivity of 5-HT[sub 1A] receptors. These preclinical tests demonstrate an antidepressant-like profile for metyrapone. Further exploration of the therapeutic potential and possible mechanism of action of glucocorticoid antagonism in depression is warranted. [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/s002130051062 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 303 Subjects: – SubjectFull: Glucocorticoids Type: general – SubjectFull: Mental depression Type: general – SubjectFull: Antidepressants Type: general – SubjectFull: Therapeutics Type: general Titles: – TitleFull: Metyrapone displays antidepressant-like properties in preclinical paradigms. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Healy, David G. – PersonEntity: Name: NameFull: Harkin, Andrew – PersonEntity: Name: NameFull: Cryan, John F. – PersonEntity: Name: NameFull: Kelly, John P. – PersonEntity: Name: NameFull: Leonard, B. E. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 10 Text: 1999 Type: published Y: 1999 Identifiers: – Type: issn-print Value: 00333158 Numbering: – Type: volume Value: 145 – Type: issue Value: 3 Titles: – TitleFull: Psychopharmacology Type: main |
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