M. Mansouri, B. Naghizadeh, B. Ghorbanzadeh, Soheila Alboghobeish, O. Cauli
Experimental Neurology, 2018
ABSTRACT Opioid‐induced neuroinflammation and the nitric oxide (NO) signal‐transduction pathway are involved in the development of opioid analgesic tolerance. The antidepressant venlafaxine (VLF) modulates NO in nervous tissues, and so we investigated its effect on induced tolerance to morphine, neuroinflammation, and oxidative stress in mice. Tolerance to the analgesic effects of morphine were induced by injecting mice with morphine (50mg/kg) once a day for three consecutive days; the effect of co‐administration of VLF (5 or 40mg/kg) with morphine was similarly tested in a separate group. To determine if the NO precursor l‐arginine hydrochloride (l‐arg) or NO are involved in the effects rendered by VLF, animals were pre‐treated with l‐arg (200mg/kg), or the NO synthesis inhibitors N(&ohgr;)‐nitro‐l‐arginine methyl ester (L‐NAME; 30mg/kg) or aminoguanidine hydrochloride (AG; 100mg/kg), along with VLF (40mg/kg) for three days before receiving morphine for another three days. Nociception was assessed with a hot‐plate test on the fourth day, and the concentration of tumor necrosis factor alpha (TNF‐&agr;), interleukin‐1beta (IL‐1&bgr;), interleukin‐6 (IL‐6), interleukin‐10, brain‐derived neurotrophic factor, NO, and oxidative stress factors such as total thiol, malondialdehyde content, and glutathione peroxidase (GPx) activity in the brain was also determined. Co‐administration of VLF with morphine attenuated morphine‐induced analgesic tolerance and prevented the upregulation of proinflammatory cytokines (TNF‐&agr;, IL‐1&bgr;, and IL‐6), NO, and malondialdehyde in brains of mice with induced morphine tolerance; chronic VLF administration inhibited this decrease in brain‐derived neurotrophic factor, total thiol, and GPx levels. Moreover, repeated administration of l‐arg before receipt of VLF antagonized the effects induced by VLF, while L‐NAME and AG potentiated these effects. VLF attenuates morphine‐induced analgesic tolerance, at least partly because of its anti‐inflammatory and antioxidative properties. VLF also appears to suppress the development of morphine‐induced analgesic tolerance through an l‐arg–NO‐mediated mechanism. HIGHLIGHTSTolerance to morphine' analgesic effect involved neuroinflammation and the nitric oxide signal‐transduction.Venlafaxine attenuated morphine‐induced analgesic tolerance.Venlafaxine prevents the upregulation of TNF‐&agr;, IL‐1&bgr;, and IL‐6, nitric oxide, and malondialdehyde.Venlafaxine inhibits the decrease in brain‐derived neurotrophic factor, total thiol, and glutathione peroxidase activity.
Cited by 19 publications.
Field of study: Medicine