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dc.contributor.authorLiebenberg, Nicoen_US
dc.contributor.authorHarvey, Brian H.en_US
dc.contributor.authorBrand, Lindaen_US
dc.contributor.authorBrink, Christiaan B.en_US
dc.date.accessioned2012-02-29T09:49:44Z
dc.date.available2012-02-29T09:49:44Z
dc.date.issued2010en_US
dc.identifier.citationLiebenberg, N. et al. 2010. Antidepressant-like properties of phosphodiesterase type 5 inhibitors and cholinergic dependency in a genetic rat model of depression. Behavioural pharmacology, 21(5-6):540-547. [http://dx.doi.org/10.1097/FBP.0b013e32833befe5]en_US
dc.identifier.issn0955-8810en_US
dc.identifier.issn1473-5849 (Online)en_US
dc.identifier.urihttp://hdl.handle.net/10394/5945
dc.identifier.urihttp://journals.lww.com/behaviouralpharm/pages/articleviewer.aspx?year=2010&issue=09000&article=00017&type=abstract
dc.identifier.urihttp://dx.doi.org/10.1097/FBP.0b013e32833befe5
dc.description.abstractWe explored the antidepressant-like properties of two phosphodiesterase type 5 (PDE5) inhibitors in a genetic animal model of depression, namely Flinders sensitive line rats. We investigated the dose-dependency of the antidepressant-like action of sildenafil, and its interaction with the cholinergic system and behavioural correlates of monoaminergic neurotransmission, in the forced swim test. Antidepressant-like properties of tadalafil (a structurally distinct PDE5 inhibitor) were also evaluated. Flinders sensitive line rats were treated for 14 days with vehicle, fluoxetine, atropine or PDE5 inhibitors±atropine. Immobility, swimming and climbing behaviours were assessed in the forced swim test. In combination with atropine (1 mg/kg), both sildenafil (10, 20 mg/kg) and tadalafil (10 mg/kg) decreased immobility while increasing swimming (serotonergic) and climbing (noradrenergic) behaviours. Interestingly, sildenafil (3 mg/kg) decreased immobility while selectively increasing climbing behaviour in the absence of atropine. These results suggest that the antidepressant-like activity of PDE5 inhibitors involve alterations in monoaminergic neurotransmission, but involve a dependence on inherent cholinergic tone so that the final response is determined by the relative extent of activation of these systems. Furthermore, the behavioural profile of sildenafil alone, and its observed antidepressant-like properties, shows strict dose-dependency, with only higher doses showing an interaction with the cholinergic system
dc.publisherWolters Kluweren_US
dc.titleAntidepressant-like properties of phosphodiesterase type 5 inhibitors and cholinergic dependency in a genetic rat model of depressionen_US
dc.contributor.researchID10066357 - Brand, Linda
dc.contributor.researchID10073892 - Brink, Christiaan Beyers
dc.contributor.researchID11083417 - Harvey, Brian Herbert
dc.contributor.researchID12262412 - Liebenberg, Nico


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