Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption

Moosavi, Maryam; Zarifkar, Amir Hossein; Farbood, Yaghoob; Dianat, Mahin; Sarkaki, Alireza; Ghasemi, Rasoul

doi:10.1016/j.ejphar.2014.03.041

Cited by 39 publications

(17 citation statements)

References 57 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: 86%

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: 86%

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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“…The neuroprotective effects of agmatine were shown in a mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease 51,52 and in cultured cerebellar granule cells and hippocampal cells submitted to glutamate and/ or NMDA-induced neurotoxicity 53,54 and corticosterone. 55 Agmatine also provides neuroprotective effects in a rat model of Alzheimer's disease induced by b-amyloid peptide (Ab fragment 25-35) 56 and protected against memory impairment induced by streptozotocin 57,58 and lipopolysaccharide (LPS). 59 The mechanims underlying these neuroprotective effects of agmatine include antiexcitotoxic, antioxidant, antiapoptotic, and pro-survival properties, [51][52][53][54][55][56][57][58][59] which may be relevant for the ability of agmatine to afford protection against neurodegenerative and psychiatric diseases.…”

Section: Agmatinementioning

confidence: 99%

Novel Targets for Fast Antidepressant Responses: Possible Role of Endogenous Neuromodulators

Camargo

Rodrigues

2019

Chronic Stress

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The available medications for the treatment of major depressive disorder have limitations, particularly their limited efficacy, delayed therapeutic effects, and the side effects associated with treatment. These issues highlight the need for better therapeutic agents that provide more efficacious and faster effects for the management of this disorder. Ketamine, an N-methyl-D-aspartate receptor antagonist, is the prototype for novel glutamate-based antidepressants that has been shown to cause a rapid and sustained antidepressant effect even in severe refractory depressive patients. Considering the importance of these findings, several studies have been conducted to elucidate the molecular targets for ketamine’s effect. In addition, efforts are under way to characterize ketamine-like drugs. This review focuses particularly on evidence that endogenous glutamatergic neuromodulators may be able to modulate mood and to elicit fast antidepressant responses. Among these molecules, agmatine and creatine stand out as those with more published evidence of similarities with ketamine, but guanosine and ascorbic acid have also provided promising results. The possibility that these neuromodulators and ketamine have common neurobiological mechanisms, mainly the ability to activate mechanistic target of rapamycin and brain-derived neurotrophic factor signaling, and synthesis of synaptic proteins in the prefrontal cortex and/or hippocampus is presented and discussed.

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“…STZ (3 mg/kg/5 l) or its vehicle (saline) was injected bilaterally in the divided doses on days 1 and 3 [10]. All microinjections were carried out in the speed of 0.5 l/min and the needle was left in the place for an additional 5 min to minimize the flow back of the solution.…”

Section: Drug Administrationmentioning

confidence: 99%

Insulin potentiates the therapeutic effect of memantine against central STZ-induced spatial learning and memory deficit

Bahramian

Rastegar

Namavar

et al. 2016

Behavioural Brain Research

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Agmatine protects against intracerebroventricular streptozotocin-induced water maze memory deficit, hippocampal apoptosis and Akt/GSK3β signaling disruption

Cited by 39 publications

References 57 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

Novel Targets for Fast Antidepressant Responses: Possible Role of Endogenous Neuromodulators

Insulin potentiates the therapeutic effect of memantine against central STZ-induced spatial learning and memory deficit

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