Repository of Research and Investigative Information

Repository of Research and Investigative Information

Dezful University of Medical Sciences

Venlafaxine inhibits naloxone-precipitated morphine withdrawal symptoms: Role of inflammatory cytokines and nitric oxide

(2019) Venlafaxine inhibits naloxone-precipitated morphine withdrawal symptoms: Role of inflammatory cytokines and nitric oxide. Metabolic Brain Disease. p. 9. ISSN 0885-7490

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Opioid-induced neuroinflammation plays a role in the development of opioid physical dependence. Moreover, nitric oxide (NO) has been implicated in several oxidative and inflammatory pathologies. Here, we sought to determine whether treatment with venlafaxine during the development of morphine dependence could inhibit naloxone-precipitated withdrawal symptoms. The involvement of neuro-inflammation related cytokines, oxidative stress, and L-arginine (L-arg)-NO pathway in these effects were also investigated. Mice received morphine (50 mg/kg/daily; s.c.), plus venlafaxine (5 and 40 mg/kg, i.p.) once a day for 3 consecutive days. In order to evaluate the possible role of L-arg-NO on the effects caused by venlafaxine, animals received L-arg, L-NAME or aminoguanidine with venlafaxine (40 mg/kg, i.p.) 30 min before each morphine injection for 3 consecutive days. On 4(th) day of experiment, behavioral signs of morphine-induced physical dependence were evaluated after i.p. naloxone injection. Then, brain levels of tissue necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), interleukin-6 (IL-6), interleukin-10 (IL-10), brain-derived neurotrophic factor (BDNF), NO and oxidative stress factors including; total thiol, malondialdehyde (MDA) contents and glutathione peroxidase (GPx) activity were determined. Co-administration of venlafaxine (40 mg/kg) with morphine not only inhibited the naloxone-precipitated withdrawal signs including jumping and weight loss, but also reduced the up-regulation of TNF-alpha, IL-1 beta, IL-6, NO and MDA contents in mice brain tissue. However, repeated administration of venlafaxine inhibited the decrease in the brain levels of BDNF, total thiol and GPx. Pre-administration of L-NAME and aminoguanidine improved, while L-arg antagonized the venlafaxine-induced effects. These results provide evidences that venlafaxine could be used as a candidate drug to inhibit morphine withdrawal through the involvement of inflammatory cytokines and l-arginine-NO in mice.

Item Type: Article
Keywords: Venlafaxine Morphine withdrawal L-arg-NO Inflammatory cytokines BDNF Oxidative stress neurotrophic factor oxidative stress tnf-alpha neuropathic pain frontal-cortex l-arginine brain tolerance expression synthase Endocrinology & Metabolism Neurosciences & Neurology
Subjects: QV Pharmacology > QV 600-666 Toxicology
Divisions: Education Vice-Chancellor Department > Faculty of Pharmacy > Department of Toxicology and Pharmacology
Page Range: p. 9
Journal or Publication Title: Metabolic Brain Disease
Journal Index: ISI
Identification Number:
ISSN: 0885-7490
Depositing User: مهندس مهدی شریفی

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