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An inhibitor of cAMP-dependent protein kinase induces behavioural and neurological antidepressant-like effects in rats

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dc.contributor.author Brink, Christiaan Beyers
dc.contributor.author Elfving, Betina
dc.contributor.author Fischer, Christina
dc.contributor.author Harvey, Brian Herbert
dc.contributor.author Liebenberg, Nico
dc.contributor.author Wegener, Gregers
dc.contributor.author Müller, Heidi Kaastrup
dc.date.accessioned 2012-11-13T10:56:06Z
dc.date.available 2012-11-13T10:56:06Z
dc.date.issued 2011
dc.identifier.citation Liebenberg, N. et al. 2011. An inhibitor of cAMP-dependent protein kinase induces behavioural and neurological antidepressant-like effects in rats. Neuroscience letters, 498(2):158-161. [http://www.journals.elsevier.com/neuroscience-letters/] en_US
dc.identifier.issn 0304-3940
dc.identifier.issn 1872-7972 (Online)
dc.identifier.uri http://hdl.handle.net/10394/7754
dc.description.abstract Although it is well established that cyclic adenosine monophosphate (cAMP) signalling via cAMPdependent protein kinase (PKA)within neurons plays an important role in depression and antidepressant treatment, the importance of several newly discovered targets that function independently from PKA, such as exchange protein activated by cAMP (Epac), remains unexplored in this regard. In this study we used a cAMP analogue that inhibits PKA but not Epac (Rp-8-Br-cAMP), to explore the modifying actions of these two targets on immobility in the forced swim test (FST) and cerebellar cAMP response element binding protein (CREB) phosphorylation in rats. In addition, we assessed central cAMP and cGMP levels and investigated the involvement of cGMP-dependent protein kinase (PKG) on any observed effects by using a selective PKG inhibitor (Rp-8-Br-PET-cGMPS).Interestingly, Rp-8-Br-cAMPS strongly reduced immobility in the FST and induced an increase in the phosphorylation of CREB in the cerebellum, effects that were unaltered by the co-administration of Rp-8-Br-PET-cGMPS. Furthermore, Rp-8-Br-cAMPS increased the accumulation of cAMP and cGMP in the hippocampus, frontal cortex and cerebellum of these rats. Together, these results suggest that in addition to activating PKA, elevated cAMP may also stimulate other targets that mediate antidepressant activity. According to the pharmacodynamic profile of Rp-8-Br-cAMPS and taking into consideration what has recently been discovered regarding the cAMP signalling system, a likely candidate is the guanine nucleotide exchange factor, Epac. en_US
dc.description.uri http://dx.doi.org/10.1016/j.neulet.2011.05.004
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.subject Depression en_US
dc.subject protein kinase A en_US
dc.subject CREB en_US
dc.subject Rp-8-Br-cAMPS en_US
dc.subject epac en_US
dc.title An inhibitor of cAMP-dependent protein kinase induces behavioural and neurological antidepressant-like effects in rats en_US
dc.type Article en_US


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