Sildenafil citrate attenuates a complex maze impairment induced by intracerebroventricular infusion of the NOS inhibitor Nω-nitro-L-arginine methyl ester

Devan, Bryan D.; Pistell, Paul J.; Daffin, Lee W.; Nelson, Christopher M.; Duffy, Kara B.; Bowker, Jonna L.; Bharati, Ila Sri; Sierra‐Mercado, Demetrio; Spangler, Edward L.; Ingram, Donald K.

doi:10.1016/j.ejphar.2007.02.008

Cited by 34 publications

(18 citation statements)

References 64 publications

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“…Only a few studies have attempted to provide direct evidence for the contribution of these cascades in the behavioral effects induced by PDE inhibition. Devan et al (2007) blocked cGMP-PKG signaling in vivo through upstream inhibition of nitric oxide synthase, and could attenuate subsequent memory impairment with a PDE5 inhibitor. In accordance with our present findings, Kroker et al (2012) were able to convert E-LTP into L-LTP by increasing cGMP via a PDE9 inhibitor, which was blocked by co-application with a PKG inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Bollen

Puzzo

Rutten

et al. 2014

Neuropsychopharmacol

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Memory consolidation is defined by the stabilization of a memory trace after acquisition, and consists of numerous molecular cascades that mediate synaptic plasticity. Commonly, a distinction is made between an early and a late consolidation phase, in which early refers to the first hours in which labile synaptic changes occur, whereas late consolidation relates to stable and long-lasting synaptic changes induced by de novo protein synthesis. How these phases are linked at a molecular level is not yet clear. Here we studied the interaction of the cyclic nucleotide-mediated pathways during the different phases of memory consolidation in rodents. In addition, the same pathways were studied in a model of neuronal plasticity, long-term potentiation (LTP). We demonstrated that cGMP/protein kinase G (PKG) signaling mediates early memory consolidation as well as early-phase LTP, whereas cAMP/protein kinase A (PKA) signaling mediates late consolidation and late-phase-like LTP. In addition, we show for the first time that early-phase cGMP/PKG signaling requires late-phase cAMP/PKA-signaling in both LTP and long-term memory formation.

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Section: Discussionmentioning

confidence: 99%

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Bollen

Puzzo

Rutten

et al. 2014

Neuropsychopharmacol

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“…On the other hand, phosphodiesterase type 5 inhibitors (PDE5-Is) affect acquisition and early consolidation processes via an increase in intracellular cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling, when administered before or directly after learning, respectively (Devan et al 2004(Devan et al , 2007Prickaerts et al 2005;Domek-Lopacinska and Strosznajder 2008;van Donkelaar et al 2008;Bollen et al 2014). Also, we found that the phosphodiesterase type 4 inhibitor (PDE4-I) rolipram, which increases cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling, improves both acquisition and late consolidation processes when administered before or at 3 h after learning (Rutten et al 2006(Rutten et al , 2007Bollen et al 2014).…”

mentioning

confidence: 99%

Possible overlapping time frames of acquisition and consolidation phases in object memory processes: a pharmacological approach

2015

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In previous studies, we have shown that acetylcholinesterase inhibitors and phosphodiesterase inhibitors (PDE-Is) are able to improve object memory by enhancing acquisition processes. On the other hand, only PDE-Is improve consolidation processes. Here we show that the cholinesterase inhibitor donepezil also improves memory performance when administered within 2 min after the acquisition trial. Likewise, both PDE5-I and PDE4-I reversed the scopolamine deficit model when administered within 2 min after the learning trial. PDE5-I was effective up to 45 min after the acquisition trial and PDE4-I was effective when administered between 3 and 5.5 h after the acquisition trial. Taken together, our study suggests that acetylcholine, cGMP, and cAMP are all involved in acquisition processes and that cGMP and cAMP are also involved in early and late consolidation processes, respectively. Most important, these pharmacological studies suggest that acquisition processes continue for some time after the learning trial where they share a short common time frame with early consolidation processes. Additional brain concentration measurements of the drugs suggest that these acquisition processes can continue up to 4-6 min after learning.

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“…[12][13][14][15] However, there has been only one study that has tested the effect of PDE5 inhibitor on cognition in human subjects, especially with psychiatric disorders. 16 In contrast with anecdotal studies, our study was conducted in healthy volunteers without psychiatric disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Erectile dysfunction was defined as an inability to attain and/or maintain a penile erection sufficient for satisfactory sexual performance. 17 The severity of erectile dysfunction was classified based on baseline IIEF erectile function domain score into mild (17)(18)(19)(20)(21), mild to moderate (12)(13)(14)(15)(16), moderate (8)(9)(10)(11) and severe (5-7). 18 The etiology of erectile dysfunction was determined by the study investigator based on patient history, as well as physical and laboratory examination findings.…”

Section: Subjectsmentioning

confidence: 99%

“…[10][11][12] Thus, some valuable animal models have been utilized to confirm the cognitive-enhancing effect of PDE5 inhibitors. Subchronic administration of sildenafil has been shown to increase cortical cGMP levels 13 and sildenafil reversed cognitive deficits in rats produced by diabetes, 14 anticholinergics 15 and hyperammonemia. 10 Despite positive findings in animal models, in vivo data are limited and no conclusive remarks can be made.…”

Section: Introductionmentioning

confidence: 99%

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Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: a pilot study

et al. 2011

Int J Impot Res

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The PDE5 inhibitors have recently been found to have cognitive-enhancing effects in animal models. To investigate the efficacy of repeated dosing with a PDE5 inhibitor on cognitive function and somatization in patients with erectile dysfunction, 27 patients with erectile dysfunction received udenafil (100 mg) at 3-day intervals for 2 months. The international index of erectile function-5 (IIEF-5), a cognitive battery (the Korean version of mini-mental state examination (K-MMSE), the frontal assessment battery (K-FAB), the Seoul verbal learning test) and a physical health questionnaire-15 (PHQ-15) were performed at baseline and at 2 months, following the administration of udenafil. The patients were divided on the basis of their IIEF-5 score into responders (change47) and non-responders. The mean IIEF-5 score was significantly increased after treatment (7.92±3.83 to 16.33±4.75, Po0.001). The scores of K-MMSE (27.03±1.58 to 28.07±1.57, P ¼ 0.001), K-FAB (13.65 ± 1.96 to 15.41 ± 1.85, Po0.001) and PHQ-15 (18.92 ± 4.96 to 17.63 ± 4.75, P ¼ 0.003) were significantly improved after treatment. In addition, the responders (n ¼ 16) had more improved cognitive function (r ¼ 0.603, P ¼ 0.001) and somatization (r ¼ À0.402, P ¼ 0.038) than non-responders (n ¼ 11). Repeated dosing with a PDE5 inhibitor seems to improve cognitive function and somatization, as well as erectile function in patients with erectile dysfunction.

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Sildenafil citrate attenuates a complex maze impairment induced by intracerebroventricular infusion of the NOS inhibitor Nω-nitro-L-arginine methyl ester

Cited by 34 publications

References 64 publications

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Improved Long-Term Memory via Enhancing cGMP-PKG Signaling Requires cAMP-PKA Signaling

Possible overlapping time frames of acquisition and consolidation phases in object memory processes: a pharmacological approach

Effects of repeated dosing with Udenafil (Zydena) on cognition, somatization and erection in patients with erectile dysfunction: a pilot study

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