GMP reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats

Rubin, Maribel Antonello; Jurach, Alexandre; Em, da Costa Júnior; Tt, Lima; Re, J; Begnini, J.; Souza, Diogo O.; Cf, de Mello

doi:10.1097/00001756-199609020-00004

Cited by 21 publications

(8 citation statements)

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“…Previously we showed that GMP also reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats (26) and is neuroprotective against QA-induced toxicity in rats (27). Guanosine also presents amnesic and anxiolytic effects in rats and mice (23,28,29).…”

Section: Discussionmentioning

confidence: 95%

Intracerebroventricular Guanine-Based Purines Protect Against Seizures Induced by Quinolinic Acid in Mice

2005

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Acute and chronic administration of the nucleoside guanosine have been shown to prevent quinolinic acid (QA) and alpha-dendrotoxin-induced seizures, as well as to impair memory and anxiety in rats and mice. In this study, we investigated the effect of i.c.v. administration of guanine-based purines (GTP, GDP, GMP, and guanosine) against seizures induced by the NMDA agonist and glutamate releaser quinolinic acid in mice. We also aimed to study the effects of the poorly hydrolysable analogs of GTP (GppNHp and GTPgammaS) and GDP (GDPbetaS) in this seizure model. QA produced seizures in 100% of mice, an effect partially prevented by guanine-based purines. In contrast to GTP (480 nmol), GDP (320-640 nmol), GMP (320-480 nmol) and guanosine (300-400 nmol), the poorly hydrolysable analogs of GTP and GDP did not affect QA-induced seizures. Thus, the protective effects of guanine nucleotides seem to be due to their conversion to guanosine. Altogether, these findings suggest a potential role of guanine-based purines for treating diseases involving glutamatergic excitotoxicity.

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Section: Discussionmentioning

confidence: 95%

Intracerebroventricular Guanine-Based Purines Protect Against Seizures Induced by Quinolinic Acid in Mice

2005

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“…In rats, bilateral cGMP (10 µg/side) or 8-bromo-cGMP (1.25 µg/side) injection into the hippocampus immediately after training improved passive avoidance retention 24 h later [79,82]. Likewise, when 8-bromo-cGMP (10 µg/side) was bilaterally injected into the hippocampus immediately after object recognition training, it improved retention performance 24 h later [81].…”

Section: Cgmpmentioning

confidence: 96%

Improving Memory: A Role for Phosphodiesterases

Blokland¹,

Schreiber

Prickaerts

2006

CPD

161

100

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During the last decennia, our understanding of the neurobiological processes underlying learning and memory has continuously improved, leading to the identification of targets for the development of memory-enhancing drugs. Here we review a class of drugs which has more recently been identified: the phosphodiesterase (PDE) inhibitors. An overview is given of the different PDEs that are known and we focus on three PDEs which have been identified as possible relevant targets for memory improvement: PDE2, PDE4 and PDE5. PDEs differ in the substrate, i.e. cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP), being hydrolyzed. Since these cyclic nucleotides have been suggested to play distinct roles in processes of memory, selective PDE inhibitors preventing the breakdown of cAMP and/or cGMP could improve memory. The present data suggest that PDE4 (cAMP) is involved in acquisition processes, although a possible role in late consolidation processes cannot be excluded. PDE5 (cGMP) is involved in early consolidation processes. Since PDE2 inhibition affects both cAMP and cGMP, PDE2 inhibitors may improve both memory processes. The field of PDEs is highly dynamic and new isoforms of PDEs are still being described. This may lead to the discovery and development of new memory enhancing drugs that selectively inhibit such isoforms. Such drugs may exert their effects only in specific brain areas and hence possess an improved side effect profile.

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“…It is well documented that glutamate plays a key role on memory mechanisms [53], and previous studies demonstrated that GMP was able to reverse the facilitatory effect of post-training intra-hippocampal glutamate administration on inhibitory avoidance task performance in rats [76]. Further studies demonstrated that GMP and guanosine are capable to modulate memory processes since pretraining administration of both guanine-based purines impaired retention of inhibitory avoidance responses in rats [20,77].…”

Section: Behavioral Effects Of Guanine-based Purinesmentioning

confidence: 97%

The Role of the Guanine-Based Purinergic System in Seizures and Epilepsy

Schmidt¹,

Souza²

2010

TONEURJ

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Guanine-based purines have been traditionally studied as modulators of intracellular processes, mainly Gprotein activity. However, more recently, several studies have shown that they exert a variety of extracellular effects not related to G-proteins, including trophic effects on neural cells, modulation of glutamatergic activity, behavioral effects and anticonvulsant activity. In this article, the putative effects of the guanine-based purines against seizures and neurotoxicity are reviewed. Current evidence suggests that guanine-based purines, especially guanosine, seem to be endogenous anticonvulsant substances, perhaps in a similar way to the adenine-based purines. Although studies addressing the mechanism of action of guanine-based purines are still lacking, their anticonvulsant activity is probably related to the modulation of several glutamatergic parameters, especially the astrocytic glutamate uptake. These findings point to the guaninebased purines as potential new targets for the development of novel drugs for neuroprotection and management of epilepsy.

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GMP reverses the facilitatory effect of glutamate on inhibitory avoidance task in rats

Cited by 21 publications

References 0 publications

Intracerebroventricular Guanine-Based Purines Protect Against Seizures Induced by Quinolinic Acid in Mice

Intracerebroventricular Guanine-Based Purines Protect Against Seizures Induced by Quinolinic Acid in Mice

Improving Memory: A Role for Phosphodiesterases

The Role of the Guanine-Based Purinergic System in Seizures and Epilepsy

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