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dc.contributor.authorBrink, C.B.
dc.contributor.authorClapton, J.D.
dc.contributor.authorEagar, B.E.
dc.contributor.authorHarvey, B.H.
dc.contributor.authorBrink, C.B.
dc.contributor.authorClapton, J.D.
dc.contributor.authorEagar, B.E.
dc.contributor.authorHarvey, B.H.
dc.date.accessioned2010-03-01T09:18:57Z
dc.date.available2010-03-01T09:18:57Z
dc.date.issued2008
dc.identifier.citationBrink, C.B. et al. 2008. Appearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studies. Journal of neural transmission, 115(1):117-125. [https://doi.org/10.1007/s00702-007-0806-5]en
dc.identifier.issn0300-9564
dc.identifier.issn1435-1463 (Online)
dc.identifier.urihttp://hdl.handle.net/10394/2847
dc.identifier.urihttps://doi.org/10.1007/s00702-007-0806-5
dc.identifier.urihttps://link.springer.com/article/10.1007%2Fs00702-007-0806-5
dc.description.abstractThe phosphodiesterase (PDE) 5 inhibitor sildenafil has been shown to display psychotropic actions in humans and animals, and has been used for the treatment of antidepressant-associated erectile dysfunction. However, its effects on the neurobiology of depression are unknown. Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) inhibition is anti-depressant in animals, and increasing cGMP with sildenafil is anxiogenic in rodents. Substantial cholinergic-nitrergic interaction exists in the brain, while sildenafil shows modulatory actions on cholinergic transmission. Depression is also associated with increased cholinergic drive. Here we report that sildenafil increases muscarinic acetylcholine receptor (mAChR) signaling in human neuroblastoma cells. We also show that fluoxetine (20 mg/kg/day × 7 days), as well as a combination of sildenafil (10 mg/kg/day × 7 days) plus the antimuscarinic atropine (1 mg/kg/day × 7 days) demonstrates significant, comparable antidepressant-like effects in the rat forced swim test (FST) and also reduces cortical β-adrenergic receptor (β-AR) density, while sildenafil or atropine alone did not. Importantly, sildenafil did not modify fluoxetine’s response. Sildenafil thus demonstrates antidepressant-like effects but only after central muscarinic receptor blockade, providing evidence for cholinergic-nitrergic interactions in the neurobiology of depression
dc.language.isoenen
dc.publisherSpringer
dc.subjectSildenafil
dc.subjectPhosphodiesterase type 5 inhibitor
dc.subjectAntidepressant
dc.subjectCyclic GMP
dc.subjectNitric oxide
dc.subjectCholinergic
dc.subjectMuscarinic acetylcholine receptor
dc.subjectRat
dc.titleAppearance of antidepressant-like effect by sildenafil in rats after central muscarinic receptor blockade: evidence from behavioural and neuro-receptor studiesen
dc.typeArticleen
dc.contributor.researchID10073892 - Brink, Christiaan Beyers
dc.contributor.researchID11083417 - Harvey, Brian Herbert
dc.contributor.researchID12299081 - Clapton, Johannes Daniël


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