Duloxetine by Modulating the Akt/GSK3 Signaling Pathways Has Neuroprotective Effects against Methamphetamine-Induced Neurodegeneration and Cognition Impairment in Rats

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Rahimi Borumand Mehrasa; MOTAGHINEJAD MAJID; MOTEVALIAN MANIJEH; GHOLAMI MINA

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Journal: Iranian Journal of Medical Sciences Year:2019 | Volume:44 | Issue:2 Page(s): 146-154

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Title

Duloxetine by Modulating the Akt/GSK3 Signaling Pathways Has Neuroprotective Effects against Methamphetamine-Induced Neurodegeneration and Cognition Impairment in Rats

Author(s)

Rahimi Borumand Mehrasa | MOTAGHINEJAD MAJID | MOTEVALIAN MANIJEH | GHOLAMI MINA | Issue Writer Certificate

Keywords

Methamphetamine

Duloxetine hydrochloride

Nerve degeneration

Cognition

Abstract

Background: The neuroprotective effects of duloxetine, as an antidepressant agent, and the neurodegenerative effects of Methamphetamine have been shown in previous studies. Nonetheless, their exact neurochemical and behavioral effects are still unclear. In the current study, we sought to clarify the molecular mechanisms involved in the protective effects of duloxetine against Methamphetamine-induced neurodegeneration. Methods: Forty adult male rats were divided randomly into 5 groups. Group 1 was the negative control and received normal saline, Group 2 was the positive control and received Methamphetamine, and Groups 3, 4, and 5 were concurrently treated with Methamphetamine (10 mg/kg) and duloxetine (5, 10, and 15 mg/kg, respectively). All the treatments were continued for 21 days. Between days 17 and 21, the Morris Water Maze (MWM) was used to assess learning and memory in the treated groups. On day 22, the hippocampus was isolated from each rat and oxidative, antioxidant, and inflammatory factors were measured. Additionally, the expression levels of the total and phosphorylated forms of the Akt and GSK3 proteins were evaluated via the ELISA method. Results: Duloxetine in all the administered doses ameliorated the effects of the Methamphetamine-induced Cognition impairment in the MWM. The chronic abuse of Methamphetamine increased malondialdehyde, tumor necrosis factor-α , and interleukin-1β , while it decreased superoxide dismutase, glutathione peroxidase, and glutathione reductase activities. Duloxetine not only prevented these malicious effects of Methamphetamine but also activated the expression of Akt (both forms) and inhibited the expression of GSK3 (both forms) in the Methamphetamine-treated rats. Conclusion: We conclude that the Akt/GSK3 signaling pathways might have a critical role in the protective effects of duloxetine against Methamphetamine-induced neurodegeneration and Cognition impairment.

Cites

Effect of acute intraperitoneal injection of Methamphetamine on the level of pain and changes in the expression of specific genes in the lumbar spinal cord of male rats

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APA: Copy

Rahimi Borumand, Mehrasa, MOTAGHINEJAD, MAJID, MOTEVALIAN, MANIJEH, & GHOLAMI, MINA. (2019). Duloxetine by Modulating the Akt/GSK3 Signaling Pathways Has Neuroprotective Effects against Methamphetamine-Induced Neurodegeneration and Cognition Impairment in Rats. IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS), 44(2), 146-154. SID. https://sid.ir/paper/758363/en

Vancouver: Copy

Rahimi Borumand Mehrasa, MOTAGHINEJAD MAJID, MOTEVALIAN MANIJEH, GHOLAMI MINA. Duloxetine by Modulating the Akt/GSK3 Signaling Pathways Has Neuroprotective Effects against Methamphetamine-Induced Neurodegeneration and Cognition Impairment in Rats. IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS)[Internet]. 2019;44(2):146-154. Available from: https://sid.ir/paper/758363/en

IEEE: Copy

Mehrasa Rahimi Borumand, MAJID MOTAGHINEJAD, MANIJEH MOTEVALIAN, and MINA GHOLAMI, “Duloxetine by Modulating the Akt/GSK3 Signaling Pathways Has Neuroprotective Effects against Methamphetamine-Induced Neurodegeneration and Cognition Impairment in Rats,” IRANIAN JOURNAL OF MEDICAL SCIENCES (IJMS), vol. 44, no. 2, pp. 146–154, 2019, [Online]. Available: https://sid.ir/paper/758363/en

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