共 53 条
Venlafaxine inhibits naloxone-precipitated morphine withdrawal symptoms: Role of inflammatory cytokines and nitric oxide
被引:20
作者:
Mansouri, Mohammad Taghi
[1
,2
]
Naghizadeh, Bahareh
[3
]
Ghorbanzadeh, Behnam
[4
]
Amirgholami, Neda
[3
]
Houshmand, Gholamreza
[5
]
Alboghobeish, Soheila
[3
]
机构:
[1] Ahvaz Jundishapur Univ Med Sci, Physiol Res Ctr, Sch Pharm, Dept Pharmacol, Ahvaz, Iran
[2] Columbia Univ, Coll Phys & Surg, Dept Anesthesiol, New York, NY 10032 USA
[3] Ahvaz Jundishapur Univ Med Sci, Toxicol Res Ctr, Sch Pharm, Dept Pharmacol, Ahvaz, Iran
[4] Dezful Univ Med Sci, Sch Med, Dept Pharmacol, Dezful, Iran
[5] Mazandaran Univ Med Sci, Sch Med, Dept Pharmacol, Sari, Iran
关键词:
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;
D O I:
10.1007/s11011-019-00491-4
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
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.
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页码:305 / 313
页数:9
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