Agmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in rats

Utkan, Tijen; Göçmez, S.S.; Regunathan, S.; Arıcıoğlu, Feyza

doi:10.1016/j.pbb.2012.07.003

Cited by 36 publications

(22 citation statements)

References 60 publications

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“…In this study, we showed that subchronic MK-801 impaired visual recognition memory even after seven days of the washout period and both agmatine and risperidone attenuated this effect of MK-801 in NORT. To our current knowledge, there is no study investigating the effect of agmatine on schizophrenia-related visual memory deficits, though several studies have shown pro-cognitive effects of agmatine in different animal models [40][41][42][43]. This is the first time that the beneficial effect of agmatine has shown on MK-801-induced visual recognition memory deficit in NORT.…”

Section: Discussionmentioning

confidence: 87%

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Ünal

Ateş

Arıcıoğlu

2018

Psychiatry and Clinical Psychopharmacology

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INTRODUCTION: Schizophrenia is one of the most severe psychiatric disorders with about 1% prevalence. It has been proved that glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonists such as MK-801 and phencyclidine cause schizophrenia-like behaviours in rodents. Agmatine is an endogenous amine synthesized from decarboxylation of arginine and has been thought to be a neurotransmitter/neuromodulator. It binds to imidazoline and alfa adrenergic receptors and blocks cation channelled receptors, such as nicotinic acetylcholine, 5-HT3 serotonergic, and NMDA receptors. It is an endogenous inhibitor of nitric oxide synthase. A limited number of studies showed that agmatine attenuates sensorimotor gating deficit, which is an important parameter for schizophrenia, and improves cognitive deficits in rats. Despite this, it has also been shown that high doses of agmatine impaired sensorimotor gating. Herein, the aim of our study is to investigate the effect of subchronic agmatine treatment on sensorimotor gating, visual recognition memory, and social functions in subchronic MK-801 model of schizophrenia in rats. METHODS: Wistar Hannover rats were divided into four groups as control (dimethyl sulphoxide), MK-801 (0.2 mg/kg), MK-801 + agmatine (20 mg/kg), and MK-801 + risperidone (0.5 mg/kg)(n = 8 per group). MK-801 was subcutaneously injected once a day for 14 days. Agmatine and risperidone were administered intraperitoneally in the last seven days of MK-801 injections. On day 14, agmatine or risperidone was injected 15 minutes before MK-801 and MK-801 15 minutes before prepulse inhibition of the acoustic startle response (PPI) test. After the seven days washout period, social interaction (SI) test and novel object recognition test (NORT) were performed. One-way analysis of variance (ANOVA) or two-way ANOVA was used for statistical evaluation of NORT, SI, and PPI, respectively. Paired Student's t-test was used for the comparison of rat's affinity to a familiar and novel object in NORT. RESULTS: MK-801 administration significantly decreased prepulse inhibition of rats in the PPI test (p < .001). In addition to this, MK-801 decreased startle response to pulse-alone trials and increased basal activity measured by the magnitude of no stimulus trials compared to the control group (p < .05). Agmatine treatment did not improve MK-801-induced PPI, startle response, or basal activity deficits while risperidone blocked the disruptive effect of MK-801 (p < .05). In NORT, the MK-801 group had significantly lower discrimination index (p < .05), whereas both the agmatine and risperidone treatments substantially increased this index (p < .01). Moreover, MK-801 injections not only decreased sniffing (p < .01) and following (p < .01) behaviours but also increased avoiding behaviour (p < .001) in SI. Agmatine partially treated social deficits (p < .001) while risperidone was reversed all of them (p < .01). CONCLUSIONS: Subchronic MK-801 administration revealed sensorimotor gating, social and cognitive deficits in rats. Subchroni...

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Section: Discussionmentioning

confidence: 87%

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Ünal

Ateş

Arıcıoğlu

2018

Psychiatry and Clinical Psychopharmacology

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“…Scopolamine has been shown to cause reversible symptoms of senile dementia in younger individuals (22). The passive avoidance task, novel object recognition test, step-down test and MWM task are used to evaluate learning and memory impairment in animals (14,23,24). …”

Section: Discussionmentioning

confidence: 99%

Effects of Fructus Akebiae on learning and memory impairment in a scopolamine-induced animal model of dementia

Wang

et al. 2014

Experimental and Therapeutic Medicine

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Fructus Akebiae (FAE) is a component of traditional Chinese medicines used for the clinical treatment of amnesia. The aim of the present study was to investigate the effects of FAE extract on scopolamine-induced learning and memory impairment in mice and Sprague-Dawley rats. Treatment with FAE (2.5, 5 and 10 mg/kg) was investigated in scopolamine-treated animals, and its effects on different types of memory were examined using the T-maze, the Morris water maze task, the novel object recognition test, the passive avoidance task and the step-down test. The results revealed that 5 and 10 mg/kg FAE attenuated scopolamine-mediated impairment of cognition, including spatial, episodic, aversive, and short- and long-term memory. Overall, these results suggest that FAE is an effective cognitive enhancer, and thus highlights the value of a multi-target strategy to address the complexity of cognitive dysfunction in Alzheimer’s disease.

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“…Our group and other research groups have repeatedly demonstrated that exogenous agmatine has a variety of pharmacological effects improving a wide spectrum of central nervous system conditions, such as algesia including neuropathic pain , mood disorders , epilepsy , morphine type addiction , neuroinjury and cognition . Perhaps one of the most well‐established effects are antistress, anxiolytic and antidepressant‐like effects produced by agmatine .…”

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confidence: 98%

Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

Şahin

Albayrak

Akdeniz

et al. 2016

Basic Clin Pharma Tox

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The activation of Nod-like receptor protein 3 (NLRP3) has lately been implicated in stress and depression as an initiator mechanism required for the production of interleukin (IL)-1b and IL-18. Agmatine, an endogenous polyamine widely distributed in mammalian brain, is a novel neurotransmitter/neuromodulator, with antistress, anxiolytic and antidepressant-like effects. In this study, we examined the effect of exogenously administered agmatine on NLRP3 inflammasome pathway/cytokine responses in rats exposed to restraint stress for 7 days. The rats were divided into three groups: stress, stress+agmatine (40 mg/kg; i.p.) and control groups. Agmatine significantly down-regulated the gene expressions of all stress-induced NLRP3 inflammasome components (NLRP3, NF-jB, PYCARD, caspase-1, IL-1b and IL-18) in the hippocampus and prefrontal cortex (PFC) and reduced pro-inflammatory cytokine levels not only in both brain regions, but also in serum. Stress-reduced levels of IL-4 and IL-10, two major anti-inflammatory cytokines, were restored back to normal by agmatine treatment in the PFC. The findings of the present study suggest that stress-activated NLRP3 inflammasome and cytokine responses are reversed by an acute administration of agmatine. Whether antidepressant-like effect of agmatine can somehow, at least partially, be mediated by the inhibition of NLRP3 inflammasome cascade and relevant inflammatory responses requires further studies in animal models of depression.

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Agmatine, a metabolite of L-arginine, reverses scopolamine-induced learning and memory impairment in rats

Cited by 36 publications

References 60 publications

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Agmatine-attenuated cognitive and social deficits in subchronic MK-801 model of schizophrenia in rats

Effects of Fructus Akebiae on learning and memory impairment in a scopolamine-induced animal model of dementia

Agmatine Reverses Sub‐chronic Stress induced Nod‐like Receptor Protein 3 (NLRP3) Activation and Cytokine Response in Rats

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