Journal of Rafsanjan University of Medical Sciences

Evaluating the Effect of Duloxetine on Morphine-Induced Dependence and Tolerance to Its Analgesic Effects in Mice
 
G. Karimi^[1], H. Ghasemzadeh[2], M.S. Alavi[3], A. Roohbakhsh[4]
 
Received: 14/11/2017  Sent for Revision: 21/01/2018    Received Revised Manuscript: 18/03/2018              Accepted: 21/04/2018
 
Background and Objectives: Despite the analgesic effects of morphine, its chronic use leads to tolerance and dependence, and duloxetine can change the rate of dependence and tolerance. This study aimed to investigate the effect of duloxetine on morphine-induced dependence and tolerance to its analgesic effects in mice.
Materials and Methods: In the present experimental study, male mice were randomly put in 37 groups of 8.  Jumping and diarrhea of the animals, at the time of withdrawal syndrome (naloxone prescription), was evaluated in two development (duloxetine±morphine) and expression (duloxetine prescription before withdrawal syndrome) factors at the 10, 20, and 30 mg/kg/bw doses of duloxetine. Moreover, open field and tail-flick test were utilized to examine the duloxetine effect on locomotor activity and tolerance to the analgesic effects of morphine, respectively. The data were analyzed using one-way analysis of variance (ANOVA) and Dunnett’s post hoc test.
Results: Duloxetine at the dose of 30 mg/kg/bw decreased jumping and locomotor activity of the animal (p<0.05), and the dose of 20 mg/kg/bw reduced both jumping  and diarrhea (p<0.05) in the expression of dependence test. At the same dose, it also reduced the animal’s locomotor activity (p<0.01) in the open field. Duloxetine at the dose of 10 mg/kg/bw was just effective in diarrhea in the development of dependence test (p<0.001). Moreover, duloxetine did not exhibit any effect on development of tolerance to analgesic effects of morphine.
Conclusion: Duloxetine reduced withdrawal signs in the expression of dependence test, but it did not have any effect on tolerance to analgesic effects of morphine.
Key words: Duloxetine, Morphine, Naloxone, Substance withdrawal syndrome, Pain, Drug tolerance, Dependence
 
Funding: This study was funded by a grant (no. 921455) from the Research Council of Mashhad University of Medical Sciences.
Conflict of interest: None declared.
Ethical approval: The Ethics Committee of Mashhad University of Medical Sciences approved the study (code: 921455).
How to cite this article: Karimi G, Ghasemzadeh H, Alavi M.S, Roohbakhsh A. Evaluating the Effect of Duloxetine on Morphine-Induced Dependence and Tolerance to Its Analgesic Effects in Mice. Univ Med Sci 2018; 17 (3): 225-40. [Farsi]