Nitric oxide role in anxiety-like behavior, memory and cognitive impairments in animal model of chronic migraine

Mohammad Reza Zarei,Mohammad Shabani,Parichehr Taheri,Farahnaz Taheri,Masoud Nazeri,Fatemeh Mohammadi,Goli Chamani,Mohsen Abedini Esfahlani

doi:10.1016/j.heliyon.2020.e05654

Mohammad Reza Zarei, Mohammad Shabani + Show 6 more

Open Access

https://doi.org/10.1016/j.heliyon.2020.e05654

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Journal: Heliyon	Publication Date: Dec 1, 2020
Citations: 17	License type: cc-by

Affiliation: Kerman University of Medical Sciences

Abstract

The occurrence of cognitive dysfunctions and anxiety and mood disorders has been shown to be higher in migraine patients. Nitric Oxide (NO) is a significant neurotransmitter in the pathophysiology of migraine, anxiety and neurodegenerative disorders. Therefore, the present study was conducted to evaluate the role of NO system in migraine-induced memory impairment and anxiety like behaviors. Nitroglycerin (NTG) was administered to the animals as an animal model of migraine and pretreatment with L-Arginine, L-NAME and saline were implemented to evaluate the role of NO system in possible cognitive impairments in animal model of migraine. Avoidance learning and memory performance, object recognition memory, anxiety-like behavior and motor activity were assessed using a shuttle box apparatus, novel object recognition, elevated plus-maze, and open field tests respectively. The data showed that the injection of nitroglycerin disturbs learning and memory and elicit anxiety like behavior in the animals. L-NAME administration suppressed the observed effect of nitroglycerin on memory and anxiety. Overall, the results indicated that nitric oxide system is implicated in memory impairments and anxiety like behavior in an animal model of migraine.

Highlights

Headache is a common neurologic disorder in the general population and approximately 90% of all headaches are primary headaches
Since nitric oxide (NO) plays an important role in pain [17] and participates in release of migraine-related factors, including substance P and prostaglandin E2 [18] which are involved in pain [19, 20], the aim of this study was to study the role of NO system in migraine-induced alterations in anxiety-like behaviors, motor function and passive avoidance learning and memory
Administration of NTG (p < 0.001; Figure 1A) and L-Arginine þ NTG (p < 0.01) significantly decreased the duration of time spent in the open arms as compared to the animals receiving saline, L-Arginine and L-NAME-treated group (L-NAME), while L-NAME treatment (p < 0.05) was able to partly ameliorate NTG effects upon this parameter

Summary

Introduction

Headache is a common neurologic disorder in the general population and approximately 90% of all headaches are primary headaches. Migraine is one of the most prevalent primary headaches associated with symptoms such as nausea, vomiting, photophobia, and phonophobia and a 5% prevalence in the general population and a significant burden for both the individual and society [1]. Migraine mechanisms have not yet been totally clarified, it has been documented that trigeminal nerve fibers surrounding meningeal vessels is involved in migraine pathophysiology [2]. NO is generated from the amino acid L-Arginine by nitric oxide synthase (NOS) in the body. The involvement of NO in learning and memory, synaptic plasticity, long-term potentiation (LTP) and the consolidation of long-term memory is demonstrated before [5]. It has been demonstrated that NO regulates activity of HPA axis and it has been implicated in regulation of anxiety and stress responses [6]

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