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dc.contributor.authorUys, Madeleine M.
dc.contributor.authorHarvey, Brian H.
dc.contributor.authorShahid, Mohammed
dc.contributor.authorSallinen, Jukka
dc.date.accessioned2017-06-19T08:42:52Z
dc.date.available2017-06-19T08:42:52Z
dc.date.issued2017
dc.identifier.citationUys, M.M. et al. 2017. The α2C-adrenoceptor antagonist, ORM-10921, exerts antidepressant-like effects in the Flinders Sensitive Line rat. Behavioural pharmacology, 28(1):9-18. [http://dx.doi.org/10.1097/FBP.0000000000000261]en_US
dc.identifier.issn0955-8810
dc.identifier.issn1473-5849 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/25036
dc.identifier.urihttps://journals.lww.com/behaviouralpharm/Abstract/2017/02000/The__2C_adrenoceptor_antagonist,_ORM_10921,_exerts.2.aspx
dc.identifier.urihttps://doi.org/10.1097/FBP.0000000000000261
dc.description.abstractDepression involves deficits in monoaminergic neurotransmission. Differential roles for α2A, B and C subtypes of the α2-adrenoceptor (AR) are evident, with selective α2C-AR antagonists purported to have antidepressant and procognitive properties. However, this has not been demonstrated in a genetic animal model of depression. The role of the α2C-AR in modulating two key depression-related behaviours in the Flinders Sensitive Line (FSL) rat was studied using a dose–response analysis following subcutaneous administration with the selective α2C-AR antagonist ORM-10921 (0.03; 0.3 mg/kg), the nonselective α2-AR antagonist idazoxan (3 mg/kg), or vehicle once daily for 14 days. Behaviour in the novel object recognition test, forced swim test (FST) and locomotor activity test was assessed. To ratify the validity of the FSL model, the reference tricyclic antidepressant imipramine (15 mg/kg, intraperitoneally) was used as a comparator drug in the FST. FSL rats demonstrated significantly increased immobility and recognition memory deficits versus Flinders Resistant Line controls, with imipramine significantly reversing said immobility. Similarly, ORM-10921 at both doses but not idazoxan significantly reversed immobility in the FST as well as attenuated cognitive deficits in FSL animals. We conclude that selective α2C-AR antagonism has potential as a novel therapeutic strategy in the treatment of depression and cognitive dysfunctionen_US
dc.language.isoenen_US
dc.publisherWolters Kluweren_US
dc.subjectα2-adrenoreceptor antagonismen_US
dc.subjectα2C selectivityen_US
dc.subjectAntidepressanten_US
dc.subjectForced swim testen_US
dc.subjectGenetic animal modelen_US
dc.subjectLearning and memoryen_US
dc.subjectProcognitiveen_US
dc.subjectRaten_US
dc.titleThe α2C-adrenoceptor antagonist, ORM-10921, exerts antidepressant-like effects in the Flinders Sensitive Line raten_US
dc.typeArticleen_US
dc.contributor.researchID11083417 - Harvey, Brian Herbert


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