Effects of the nitric oxide donor molsidomine on different memory components as assessed in the object-recognition task in the rat

Pitsikas, Nikolaos; Rigamonti, Antonello E.; Cella, Silvano G.; Müller, Eugenio E.

doi:10.1007/s00213-002-1090-6

Cited by 38 publications

(10 citation statements)

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“…in a volume of 0.5 ml per rat. Doses of molsidomine were chosen based on studies in which they were effective against learning impairments and did not produce adverse side effects (hypotension, sensorimotor deficits) (Meyer et al, 1998; Pitsikas et al, 2001, 2002a, b, 2003, 2005). Doses of compounds are expressed as bases.…”

Section: Methodsmentioning

confidence: 99%

“…Among NO donors, molsidomine has a high bioavailability, a long‐lasting duration of action (Boger et al, 1994) likely crosses the blood‐brain barrier (BBB) (Maccario et al, 1997; Rigamonti et al, 2001) and increases its permeability (Mayhan, 2000). Molsidomine was found effective to antagonize memory deficits in different animal models (Meyer et al, 1998; Pitsikas et al, 2001, 2002a, b, 2003, 2005).…”

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confidence: 99%

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Nitric oxide donor molsidomine attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801

2006

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There is experimental evidence indicating that the non-competitive NMDA receptor antagonist MK-801 impairs cognition and produces a series of schizophrenia-like symptoms in rodents (hypermotility, stereotypies, and ataxia). The present study was designed to investigate the efficacy of the nitric oxide (NO) donor molsidomine in counteracting these MK-801-induced behavioral effects in the rat. In a first study, post-training administration of molsidomine (at 4 but not 2 mg/kg) successfully antagonized MK-801-induced performance deficits in a recognition memory test. In a subsequent study, molsidomine (2 and 4 mg/kg) was shown to be unable to reverse MK-801-induced hypermotility but attenuated stereotypies (continuous movement whole cage, body sway, and head weaving) produced by MK-801. Moreover, at 4 mg/kg this NO donor counteracted MK-801-induced ataxia. Our findings indicate that molsidomine attenuates behavioral effects related to the hypofunction of the NMDA receptor suggesting that NO might be involved in the psychotomimetic effects of non-competitive NMDA receptor antagonists.

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Section: Methodsmentioning

confidence: 99%

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Nitric oxide donor molsidomine attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801

2006

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“…This could lead to overlearning of environmental cues and contamination of the task by reference memory. To try to prevent this phenomenon, we chose a 24-h intertrial delay because it was previously shown that this duration made discrimination more difficult for control rats (63).…”

Section: Object Recognitionmentioning

confidence: 99%

A 5‐Month Period of Epilepsy Impairs Spatial Memory, Decreases Anxiety, but Spares Object Recognition in the Lithium‐pilocarpine Model in Adult Rats

Détour

Schroeder²,

Desor³

et al. 2005

Epilepsia

122

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Summary:Purpose: In temporal lobe epilepsy (TLE), interictal behavioral disorders affect patients' quality of life. Therefore we studied long-term behavioral impairments in the lithiumpilocarpine (li-pilo) model of TLE.Methods: Eleven li-pilo adult rats exhibiting spontaneous recurrent seizures (SRSs) during 5 months were compared with 11 li-saline rats. Spatial working memory was tested in a radial arm maze (RAM), anxiety in an elevated plus-maze (EPM), and nonspatial working memory in an object-recognition paradigm. Neuronal loss was assessed on thionine brain sections after behavioral testing.Results: In the RAM, the time to complete each session and the number of errors per session decreased over a 5-day period in li-saline rats but remained constant and significantly higher in li-pilo rats. In the EPM, the number of entries in and time spent on open arms were significantly higher in li-pilo than li-saline rats. In the object-recognition task, the two groups exhibited a comparable novelty preference for the new object. Neuronal loss reached 47-90% in hilus, CA1, amygdala, and piriform and entorhinal cortex.Conclusions: In li-pilo rats having experienced SRS for 5 months, performance in the object-recognition task is spared, which suggests that object discrimination remains relatively intact despite extensive damage. Neuronal loss in regions mediating memory and anxiety, such as hippocampus, entorhinal cortex, and amygdala, may relate to impaired spatial orientation and decreased anxiety. Key Words: Temporal lobe epilepsyLithium-pilocarpine-Spatial memory-Object recognitionAnxiety-Neuronal damage.It is generally agreed that patients with temporal lobe epilepsy (TLE) are more prone to behavioral disorders and cognitive impairments than is the general population (1). These interictal impairments usually disrupt the patient's everyday life, often more than the seizures themselves (2,3). Furthermore, depression or anxiety often develops several years after epilepsy onset (2,4), and the control of the seizures with pharmacologic treatment does not always suppress these disorders (5). Among cognitive impairments, memory problems are frequently observed in patients with TLE. The most reliable observations are deficits in declarative memory (ability to acquire facts and events related to one's personal past, 6) and in the performance of visuospatial tasks (7-9). Moreover, long duration of refractory TLE seems to be associated with cognitive deterioration (10-12). Thus understanding the neural mechanism underlying these disturbances is an important Accepted November 28, 2004. Address correspondence and reprint requests to Dr. J. Detour at INSERM U666, Clinique Psychiatrique, Hôpitaux Universitaires, 1 place de l'hôpital, BP426, 67091 Strasbourg Cedex, France. E-mail: Julien.Detour@chru-strasbourg.fr issue in the management of TLE. In animal models of TLE, the molecular, lesional, and metabolic characteristics have been quite extensively studied. Conversely, the cognitive or behavioral validity of the models was less s...

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“…Normally, animals can discriminate between familiar and novel objects (exploration, novel > familiar object) at T2 30‐min . However, discrimination is generally attenuated at T2 24‐h (similar exploration duration for both the objects) (Ennaceur et al, ; Bartolini et al, ; Pitsikas et al, ). In the present study also, untreated control rats showed intact memory at T2 30‐min , but deficit at T2 24‐h .…”

Section: Discussionmentioning

confidence: 99%

Pro‐cognitive action of CART is mediated via ERK in the hippocampus

et al. 2016

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Although cocaine- and amphetamine-regulated transcript peptide (CART) is detected in several cortical and subcortical areas, its role in higher functions has been largely ignored. We examined the significance of CART in memory formation and tested if the downstream actions of CART involve N-methyl-d-aspartate (NMDA) activated extra-cellular signal-regulated kinase (ERK). Newly formed memory was evaluated using novel object recognition test consisting of familiarization (T1) and choice trials (T2). The choice trials were performed at two time points: 30-min (T230-min ) and 24-h (T224-h ) postacquisition. In choice trial (T230-min ), vehicle control rats explored the novel object for significantly longer duration than the familiar object indicating intact memory formation. However, CART-antibody, U0126 [ERK antagonist, both via intracerebroventricular (icv) or intrahippocampal (ih) route] or MK-801 (NMDA antagonist; intraperitoneal) treated rats spent less time exploring novel objects; CART peptide (icv or ih) was ineffective. During choice trial at T224-h , a significant decrease in novel object exploration time was noticed in vehicle control rats suggesting amnesia. However, treatment with CART, prior to familiarization trial (T1), promoted exploration of the novel object even at T224-h . Pretreatment with U0126 or MK-801 blocked pro-cognitive-like effect of CART suggesting involvement of NMDA-ERK pathway in CART's action. Animals subjected to the object familiarization trial showed a drastic increase in the CART-immunoreactivity in the cells of cornu ammonis 3 and polymorph layer of dentate gyrus, and fibers within ento- (ENT) and peri-rhinal (PRH) cortices. Western blot analysis revealed that CART treatment significantly up-regulated the expression of phospo-ERK1/2 in hippocampus, ENT and PRH. This effect was attenuated following pretreatment with U0126 or MK-801, suggesting the activation of ERK signaling cascade through NMDA receptors. Thus, CART system seems to play an important role in recognition memory and that these effects may be mediated by NMDA receptors-ERK signaling in the ENT/PRH-hippocampal circuit. © 2016 Wiley Periodicals, Inc.

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Effects of the nitric oxide donor molsidomine on different memory components as assessed in the object-recognition task in the rat

Abstract: These results indicate that the NO donor molsidomine may modulate different aspects of memory.

Cited by 38 publications

References 49 publications

Nitric oxide donor molsidomine attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801

Nitric oxide donor molsidomine attenuates psychotomimetic effects of the NMDA receptor antagonist MK-801

A 5‐Month Period of Epilepsy Impairs Spatial Memory, Decreases Anxiety, but Spares Object Recognition in the Lithium‐pilocarpine Model in Adult Rats

Pro‐cognitive action of CART is mediated via ERK in the hippocampus

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