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dc.contributor.authorLiebenberg, Nicoen_US
dc.contributor.authorHarvey, Brian Herberten_US
dc.contributor.authorBrink, Christiaan Beyersen_US
dc.contributor.authorWegener, Gregersen_US
dc.identifier.citationLiebenberg, N. et al. 2010. Investigating the role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonism. Behavioural brain research, 209(1):137-141. []en_US
dc.description.abstractThe cGMP/PK-G pathway plays a crucial role in neuroprotection and neurotrophin support, and is possibly involved in antidepressant action. Recently we reported on a novel antidepressant-like response following simultaneous administration of sildenafil (phosphodiesterase 5 (PDE5) inhibitor, thereby increasing cGMP levels), and atropine (muscarinic acetylcholine receptor antagonist) in the rat forced swim test (FST). However, it is unclear whether the antidepressant-like activity of sildenafil + atropine is mediated via the activation of PK-G, an important down-stream effector for cGMP, and whether this may target known pathways in antidepressant action. We investigated whether the antidepressant-like response of sildenafil ± atropine could be reversed by Rp-8-Br-PET-cGMP, a PK-G inhibitor, and also whether a combination of 8-Br-cGMP (PK-G activator) ± atropine would likewise be active in the FST, and whether this combination could be attenuated by a PK-G inhibitor. 8-Br-cGMP alone, but not sildenafil alone, reduced immobility and selectively increased swimming in the FST. The antidepressant-like action of sildenafil was only evident following co-administration of atropine, and selectively increased climbing behaviour. Importantly, PK-G inhibition prevented the antidepressant-like effects of both 8-Br-cGMP and the sildenafil/atropine combination. These results confirm cholinergic-cGMP–PK-G interactions in the antidepressant-like effects of sildenafil, putatively acting via noradrenergic mechanisms, whereas direct PK-G activation induces antidepressant-like effects that are associated with enhancement of serotonergic neurotransmission
dc.subjectPhosphodiesterase 5
dc.subjectcGMP-dependent protein kinase
dc.subjectForced swim test
dc.titleInvestigating the role of protein kinase-G in the antidepressant-like response of sildenafil in combination with muscarinic acetylcholine receptor antagonismen_US
dc.contributor.researchID11083417 - Harvey, Brian Herbert
dc.contributor.researchID10073892 - Brink, Christiaan Beyers

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