Involvement of NO/NMDA-R pathway in the behavioral despair induced by amphetamine withdrawal

Authors

Arvin Haj-Mirzaian, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Shahid Beheshti Universtiy of Medical Sciences, Tehran, Iran.
Shayan Amiri, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Regenerative Medicine Program, Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
Hossein Amini-Khoei, Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran; Department of Physiology and Pharmacology, School of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.
Arya Haj-Mirzaian, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Arsalan Hashemiaghdam, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Kiana Ramezanzadeh, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Shahid Beheshti Universtiy of Medical Sciences, Tehran, Iran.
Maria Ghesmati, Department of Microbiology, Islamic Azad University of Lahijan, Lahijan, Iran.
Khashayar Afshari, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Ahmad Reza Dehpour, Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpoura@sina.tums.ac.ir.

Document Type

Article

Publication Title

Brain research bulletin

Abstract

Abrupt discontinuation of chronic amphetamine consumption leads to withdrawal symptoms including depression, anhedonia, dysphoria, fatigue, and anxiety. These irritating symptoms may result in continuing to take the drug or can lead to suicidal behavior. Past studies have shown the involvement of various biologic systems in depression induced following amphetamine withdrawal (AW). However, there is no evidence about the relation between nitric oxide (NO) with NMDA receptors on depression following AW. In this study, we examined the involvement of the NO/NMDA pathways on depressive-like behaviors after 24 h withdrawal following 5 continuous days of amphetamine administration in male NMRI mice. Behavioral tasks used for depression assessment included the forced swimming test (FST), the Splash test and the open field test (OFT). In order to evaluate the role of NO/NMDA pathways animals treated with MK-801 (NMDA-R antagonist), Aminoguanidine (AG), a selective iNOS inhibitor, Nω-Nitro-l-arginine (L-NNA), a non-selective NOS inhibitor and 7-Nitro indazole (7-NI), a selective nNOS inhibitor. We also measured the level of nitrite in the hippocampus. Our data showed that AW induced the depressive-like effect in the FST and the Splash test. We showed that administration of AG, L-NNA, and MK-801 mitigated AW induced depression, however, 7-NI was failed to decrease depressive-like behaviors. Also, the antidepressant-like effect of co-injection of sub-effective doses of MK-801 with AG suggested that inducible nitric oxide synthase (iNOS) is associated with NMDA-R in AW induced depression. In conclusion, both NO and NMDA-R pathways are involved and related to each other in depression induced following AW.

First Page

81

Last Page

90

DOI

10.1016/j.brainresbull.2018.02.001

Publication Date

5-1-2018

Recommended Citation

Haj-Mirzaian, Arvin; Amiri, Shayan; Amini-Khoei, Hossein; Haj-Mirzaian, Arya; Hashemiaghdam, Arsalan; Ramezanzadeh, Kiana; Ghesmati, Maria; Afshari, Khashayar; and Dehpour, Ahmad Reza, "Involvement of NO/NMDA-R pathway in the behavioral despair induced by amphetamine withdrawal" (2018). Internal Medicine. 324.
https://scholar.bridgeporthospital.org/internal_medicine/324

Identifier

29421244 (pubmed); 10.1016/j.brainresbull.2018.02.001 (doi); S0361-9230(17)30615-9 (pii)