Simultaneous use of venlafaxine and calcium channel blockers on tolerance to morphine: The role of mitochondrial damage and oxidative stress in the brain.

Autor: Soleimanii A; School of medicine, Student Research Committee, Dezful University of Medical Sciences, Dezful, Iran., Fallah F; School of medicine, Student Research Committee, Dezful University of Medical Sciences, Dezful, Iran., Ghorbanzadeh B; Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran., Oroojan AA; Department of Physiology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran., Amirgholami N; Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran., Alboghobeish S; Department of Pharmacology, School of Medicine, Dezful University of Medical Sciences, Dezful, Iran. Electronic address: Alboghobeish.s@dums.ac.ir.
Jazyk: angličtina
Zdroj: Pharmacology, biochemistry, and behavior [Pharmacol Biochem Behav] 2024 Dec; Vol. 245, pp. 173864. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1016/j.pbb.2024.173864
Abstrakt: Background: One of the reasons for tolerance to morphine is increased oxidative stress and dysfunction of cell mitochondria in the hippocampus. Venlafaxine and calcium channel blockers can protect mitochondrial function. The investigation of the role of mitochondrial damage and oxidative stress in the simultaneous use of venlafaxine and calcium channel blockers on the acute analgesic effects of morphine and the induction of tolerance to its effects in mice was assessed.
Method: In this experimental study, to induce tolerance to morphine, NMRI mice were treated with 50 mg/kg morphine for three consecutive days and 5 mg/kg morphine on the fourth day. Venlafaxine (20 mg/kg) alone or in combination with calcium channel blockers, nimodipine (10 mg/kg), and diltiazem (40 mg/kg) was administered 30 min before morphine, and the hot plate test was used. Then, hippocampal mitochondria were isolated by differential centrifugation method, and the levels of mitochondrial dehydrogenase activity, mitochondrial membrane potential, mitochondrial ROS production rate, as well as the content of glutathione and malondialdehyde in hippocampal mitochondria, were measured.
Results: The administration of venlafaxine-nimodipine and venlafaxine-diltiazem increased morphine's acute analgesic effects (P < 0.05) and reduced the induction and expression of tolerance to the analgesic effects of morphine (P < 0.05). Morphine significantly decreased MTT and GSH and increased MDA, mitochondrial membrane damage, and ROS compared to the control group (P < 0.01). Injection of venlafaxine-nimodipine and also venlafaxine-diltiazem 30 min before morphine can improve these alterations (P < 0.05).
Discussion and Conclusion: Our data showed that the simultaneous use of venlafaxine with calcium channel blockers could increase the acute analgesic effects of morphine and reduce the induction and expression of tolerance to it. Also, the preventive and protective roles of simultaneous administration of venlafaxine and calcium channel blockers on morphine-induced mitochondrial oxidative stress and damage during the tolerance test were achieved.
Competing Interests: Declaration of competing interest There is nothing to declare.
(Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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