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Fadaei-Kenarsary M, Farbood Y, Taghi Mansouri SM, et al. Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats. Basic Clin Neurosci. 2015;6(1):21-8
Fadaei-Kenarsary, M., Farbood, Y., Taghi Mansouri, S. M., & Fathi Moghaddam, H. (2015). Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats. Basic and clinical neuroscience, 6(1), 21-8.
Fadaei-Kenarsary, Meisam, et al. "Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats." Basic and clinical neuroscience vol. 6,1 (2015): 21-8.
Fadaei-Kenarsary M, Farbood Y, Taghi Mansouri SM, Fathi Moghaddam H. Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats. Basic Clin Neurosci. 2015 Jan;6(1):21-8. PMID: 27504153; PMCID: PMC4741273.
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Basic Clin Neurosci. 2015 Jan;6(1):21-8.

Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats.

Basic and clinical neuroscience

Meisam Fadaei-Kenarsary, Yaghoob Farbood, Seyed Mohammad Taghi Mansouri, Hadi Fathi Moghaddam

Affiliations

  1. Department of Physiology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences (AJUMS), Ahvaz, Iran; Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
  2. Physiology Research Center, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Pharmacology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

PMID: 27504153 PMCID: PMC4741273

Abstract

INTRODUCTION: Methadone has been used as a drug to detoxify opioid tolerance. Naloxane precipitated morphine withdrawal behaviours were attenuated by venlafaxine as an antidepressant. On the contrary, after detoxifying the opioids, spontaneous withdrawal syndrome may occur with pain sensitivity. Therefore the present study aimed to examine the effects of chronic methadone (70 mg/kg, in drinking water, 7 days), venlafaxine (80 mg/kg/day, intraperitoneally, 7 days) and their combinations with the spontaneous morphine withdrawal syndrome and pain sensitivity.

METHODS: Twenty eight young male Sprague-Dawley rats were randomly divided into 4 groups: control, venlafaxine treated, methadone treated and venlafaxine + methadone treated. Morphine sulfate (10 mg/kg/day, subcutaneously, 4 days) was injected to all animals. Then primary withdrawal behaviours and tail flick test were performed. The test was then followed by methadone or its vehicle administration. Second intervention was venlafaxine or its vehicle injection. Then final withdrawal behaviours and tail flick test were performed.

RESULTS: Combination of chronic methadone substitution and venlafaxine administration, significantly reduced freezing behaviour of spontaneous morphine withdrawal syndrome (P<0.01, 379±144%). Chronic methadone administration (P<0.05, 35±8% difference with venlafaxine treated group) induced hyperalgesia. A positive correlation (P=0.001, +63%) was observed between the animals final freezing scores and their response latencies to the painful stimulus.

DISCUSSION: Combination of chronic methadone and venlafaxine administrations reduces freezing withdrawal behaviour. Further investigations on analgesic interventions are needed to overcome this hyperalgesia.

Keywords: Methadone; Morphine Withdrawal Syndrome; Pain; Rat; Venlafaxine

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