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

Haj-Mirzaian, Arvin. and Amiri, Shayan. and Amini-Khoei, Hossein. and Haj-Mirzaian, Arya. and Hashemiaghdam, Arsalan. and Ramezanzadeh, Kiana. and Ghesmati, Maria. and Afshari, Khashayar. and Dehpour, Ahmad Reza. (2018) Involvement of NO/NMDA-R pathway in the behavioral despair induced by amphetamine withdrawal. Brain Research Bulletin, 139.

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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. © 2018

Item Type: Article
Uncontrolled Keywords: Amphetamine withdrawal,Behavioral despair,NO/NMDA-R pathway
Subjects: WM Psychiatry
QV pharmacology
Divisions: Faculty of Medicine > Department of Clinical Sciences > Department of pharmacology
Faculty of Medicine > School of Psychology
Reserach Vice-Chancellar Department > Medical Plants Research Center
Depositing User: Users 1 not found.
Date Deposited: 01 Sep 2018 09:06
Last Modified: 01 Sep 2018 09:06

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