Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats

Heiberg, Ida Louise; Wegener, Gregers; Rosenberg, Raben

doi:10.1016/s0166-4328(02)00084-0

Cited by 127 publications

(65 citation statements)

References 41 publications

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“…NO activates guanylate cyclase that produces cGMP, and cGKII is a downstream signaling target of cGMP (Rameau et al 2007;Serulle et al 2007;Ota et al 2008;Kim et al 2015a). Several studies suggest that the inhibition of both nNOS and guanylate cyclase shows antidepressant-like effects (Eroglu and Caglayan 1997;Heiberg et al 2002;Kaster et al 2005;Joca and Guimaraes 2006;Jesse et al 2008;Zomkowski et al 2010). Therefore, we hypothesized that cGKII KO would have the same antidepressant effects as those inhibitors, via alteration of GluA1-mediated synaptic transmission.…”

Section: Cgkii Ko Animals Show Less Depression-like Behaviorsmentioning

confidence: 96%

Brain region-specific effects of cGMP-dependent kinase II knockout on AMPA receptor trafficking and animal behavior

et al. 2016

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Phosphorylation of GluA1, a subunit of AMPA receptors (AMPARs), is critical for AMPAR synaptic trafficking and control of synaptic transmission. cGMP-dependent protein kinase II (cGKII) mediates this phosphorylation, and cGKII knockout (KO) affects GluA1 phosphorylation and alters animal behavior. Notably, GluA1 phosphorylation in the KO hippocampus is increased as a functional compensation for gene deletion, while such compensation is absent in the prefrontal cortex. Thus, there are brain region-specific effects of cGKII KO on AMPAR trafficking, which could affect animal behavior. Here, we show that GluA1 phosphorylation levels differ in various brain regions, and specific behaviors are altered according to region-specific changes in GluA1 phosphorylation. Moreover, we identified distinct regulations of phosphatases in different brain regions, leading to regional heterogeneity of GluA1 phosphorylation in the KO brain. Our work demonstrates region-specific changes in GluA1 phosphorylation in cGKII KO mice and corresponding effects on cognitive performance. We also reveal distinct regulation of phosphatases in different brain region in which region-specific effects of kinase gene KO arise and can selectively alter animal behavior.

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Section: Cgkii Ko Animals Show Less Depression-like Behaviorsmentioning

confidence: 96%

Brain region-specific effects of cGMP-dependent kinase II knockout on AMPA receptor trafficking and animal behavior

et al. 2016

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“…For example, depressed patients exhibit elevated plasma nitrate levels (9), whereas pre-clinical studies have demonstrated antidepressant-like effects following the local or systemic administration of NOS inhibitors (10)(11)(12)(13)(14)(15)(16). Furthermore, the Glu/NMDAR/NO/cGMP pathway has been shown to be involved in the antidepressantlike activity of a range of different drugs using rodent models (11)(12)(13)(17)(18)(19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression

Liebenberg

Joca

Wegener

2014

Acta Neuropsychiatr.

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Liebenberg N, Joca S, Wegener G. Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression.Objective: We investigated whether the nitric oxide (NO) precursor, L-arginine, can prevent the antidepressant-like action of the fast-acting antidepressant, ketamine, in a genetic rat model of depression, and/or induce changes in the glutamate (Glu)/N-methyl-D-aspartate receptor (NMDAR)/NO/cyclic guanosine monophosphate (cGMP) signalling pathway. Hereby it was evaluated whether the NO signalling system is involved in the antidepressant mechanism of ketamine. Methods: Flinders sensitive line (FSL) rats received single i.p. injections of ketamine (15 mg/kg) with/without pre-treatment (30 min prior) with L-arginine (500 mg/kg). Depression-like behaviour was assessed in the forced swim test (FST) in terms of immobility, and the activation state of the Glu/NMDAR/NO/cGMP pathway was evaluated ex vivo in the frontal cortex and hippocampus regions in terms of total constitutive NOS (cNOS) activity and cGMP concentration. Results: L-Arginine pre-treatment prevented the antidepressant-like effect of ketamine in the FST, as well as a ketamine-induced increase in cGMP levels in the frontal cortex and hippocampus of FSL rats. Ketamine reduced cNOS activity only in the hippocampus, and this effect was not reversed by L-arginine. Conclusion: Both the behavioural and molecular results from this study indicate an involvement for the NO signalling pathway in the antidepressant action of ketamine. Although not easily interpretable, these findings broaden our knowledge of effects of ketamine on the NO system. Signficant outcomes• The behavioural results indicate the involvement of the nitric oxide (NO) signalling system in the antidepressant-like action of ketamine;• The molecular data reveals ketamine-induced changes in NO signalling in the frontal cortex and hippocampus, and indicates that increased cyclic guanosine monophosphate (cGMP) levels may be important for the antidepressant action of ketamine. Limitations• The behavioural test used in this study is not appropriate for the evaluation of onset of action of antidepressants, and the results can therefore not reveal whether NO signalling is specifically involved in the time of onset of ketamine's antidepressant effect.• The observation that L-arginine on its own did not increase, but instead decreased constitutive NOS (cNOS) activity in both brain regions tested, complicates the interpretation of the results. 90https://www.cambridge.org/core/terms. https://doi

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“…In contrast, c-PTIO administration into the PL reduced locomotor activity during the first minute of the open field test. However, similar effects have been previously described following systemic administration of both NOS inhibitors and imipramine (Heiberg et al 2002;Harkin et al 2003;Gigliucci et al 2010). Since this reduction in the immobility period, the FST was seen after the same dose of c-PTIO, this Fig.…”

Section: Discussionsupporting

confidence: 83%

“…Moreover, systemic administration of ODQ, a sGC inhibitor, in rodents induces similar antidepressant-like effects (Heiberg et al 2002). More recently, Li and colleagues (Li et al 2006) reported that cultured cells treated with conventional antidepressants presented an attenuated response to NMDAR-and NO-mediated signaling, therefore, suggesting that this could be part of antidepressant-induced effects.…”

mentioning

confidence: 99%

Participação da via NMDA-NO do córtex pré-frontal medial ventral na modulação das consequências comportamentais do estresse de nado forçado: mecanismos intracelulares

Pereira¹

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A minha orientadora, professora Dr a . Sâmia Regiane Lourenço Joca, por todo apoio e confiança em mim depositados e, principalmente, pela excelente orientação.Ao professor Dr. Francisco Silva Guimarães, pelas discussões em seminários e pelo espaço cedido em seu laboratório.Ao professor Dr. Leonardo Resstel, pelo apoio, discussões e conselhos sobre o projeto, sem esquecer os churrascos muito bem preparados por ele.Ao professor Dr. Gregers Wegener, da Universidade de AarhusDinamarca, por ter me aceitado para realização de estágio no exterior em seu laboratório e por todo aprendizado obtido nessa excelente oportunidade.Ao Vinicius Sato, grande amigo do laboratório e de todo meu tempo em Ribeirão Preto, pela ajuda, pelas conversas e discussões.Aos amigos e amigas do laboratório, Laura A. S., Laura L., Cassiano, Karina, Ariandra, Deidiane, Murilo, Rafaela, Izaque e Aline pela ótima convivência.À nossa técnica do laboratório Flávia Sallata, pela ajuda no dia a dia do laboratório. Aos técnicos José Carlos e Eleni, do laboratório do professor Francisco S. Guimarães, por toda a ajuda.As secretárias Sonia, Fátima, Marlene e ao José Waldik Ramon por todos os esclarecimentos, ajuda com documentação e também pelos conselhos. A dona Nina por toda a ajuda no laboratório.

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Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats

Cited by 127 publications

References 41 publications

Brain region-specific effects of cGMP-dependent kinase II knockout on AMPA receptor trafficking and animal behavior

Brain region-specific effects of cGMP-dependent kinase II knockout on AMPA receptor trafficking and animal behavior

Nitric oxide involvement in the antidepressant-like effect of ketamine in the Flinders sensitive line rat model of depression

Participação da via NMDA-NO do córtex pré-frontal medial ventral na modulação das consequências comportamentais do estresse de nado forçado: mecanismos intracelulares

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