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dc.contributor.authorBrand, Sarel Jacobus
dc.contributor.authorHarvey, Brian Herbert
dc.date.accessioned2016-10-20T12:37:30Z
dc.date.available2016-10-20T12:37:30Z
dc.date.issued2017
dc.identifier.citationBrand, S.J. & Harvey, B.H. 2017. Exploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression. II. Response to antidepressant augmentation strategies. Acta neuropsychiatrica, 29(4):207-221. [https://doi.org/10.1017/neu.2016.50]en_US
dc.identifier.issn0924-2708
dc.identifier.issn1601-5215 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/19117
dc.identifier.urihttps://doi.org/10.1017/neu.2016.50
dc.identifier.urihttps://www.cambridge.org/core/product/7901BDB174FA407D2E8B2AB8185EDE48
dc.description.abstractPost-traumatic stress disorder (PTSD) displays high co-morbidity with major depression and treatment-resistant depression (TRD). Earlier work demonstrated exaggerated depressive-like symptoms in a gene×environment model of TRD and an abrogated response to imipramine. We extended the investigation by studying the behavioural and monoaminergic response to multiple antidepressants, viz. venlafaxine and ketamine with/without imipramine. Male Flinders sensitive line (FSL) rats, a genetic model of depression, were exposed to a time-dependent sensitisation (TDS) model of PTSD and compared with stress naive controls. 7 days after the TDS procedures, immobility and coping (swimming and climbing), behaviours in the forced swim test (FST) as well as hippocampal and cortical 5-hydroxyindoleacetic acid (5HIAA) and noradrenaline (NA) levels were analysed. Response to imipramine, venlafaxine and ketamine treatment (all 10 mg/kg×7 days) alone and in combination were subsequently studied. TDS exacerbated depressive-like behaviour of FSL rats in the FST. Imipramine, venlafaxine and ketamine were ineffective as monotherapy in TDS-exposed FSL rats. However, combining imipramine with either venlafaxine or ketamine resulted in significant anti-immobility effects and enhanced coping behaviours. Only ketamine+imipramine (frontal-cortical 5HIAA and NA), ketamine alone (frontal-cortical and hippocampal NA) and venlafaxine+imipramine (frontal-cortical NA) altered monoamine responses versus untreated TDS-exposed FSL rats. Exposure of FSL rats to TDS inhibits antidepressant response at behavioural and neurochemical levels. Congruent with TRD, imipramine plus venlafaxine or ketamine overcame treatment resistance in these animals. These data further support the hypothesis that exposure of FSL rats to a PTSD-like paradigm produces a valid animal model of TRD and warrants further investigationen_US
dc.language.isoenen_US
dc.publisherCambridge Univ Pressen_US
dc.subjectAnimal modelen_US
dc.subjectNMDA antagonisten_US
dc.subjectNoradrenaline reuptake inhibitoren_US
dc.subjectSerotonin reuptake inhibitoren_US
dc.subjectStress re-stressen_US
dc.titleExploring a post-traumatic stress disorder paradigm in Flinders sensitive line rats to model treatment-resistant depression. II. Response to antidepressant augmentation strategiesen_US
dc.typeArticleen_US
dc.contributor.researchID11083417 - Harvey, Brian Herbert
dc.contributor.researchID20279477 - Brand, Sarel Jacobus


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