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Drug Res (Stuttg) 2014; 64(08): 393-398
DOI: 10.1055/s-0033-1358728
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Duloxetine Attenuated Morphine Withdrawal Syndrome in the Rat

M. Charkhpour
1   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
R. M. Jafari
1   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
H. Ghavimi
2   Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3   Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
S. Ghanbarzadeh
3   Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
4   Research Center for Pharmaceutical Nanotechnology and Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
,
A. Parvizpur
1   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
5   Drug Applied Research Center, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 17 September 2013

accepted 24 October 2013

Publication Date:
21 November 2013 (online)

Also available at
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Abstract

Background:

Long term exposure to morphine can induce dependence. The exact mechanisms of dependence are not yet fully understood. Many studies have been conducted to find new drugs that can prevent dependence. This study examined the effects of the chronic administration of duloxetine on the morphine withdrawal syndrome in rats.

Methods:

To this end, male Wistar rats (170–220 g) were randomly divided into 5 groups including one saline treated group (non-depend­ent group) and 4 morphine dependent groups. The experimental groups received additive doses of morphine for 9 days in order to induce dependence according to the following protocol: day 1: 5 mg/kg/12 h, days 2 and 3: 10 mg/kg/12 h, days 4, 5: 15 mg/kg/12 h, days 6 and 7: 20 mg/kg/12 h and days 8 and 9: 25 mg/kg/12 h. On the ninth day, the morning dose of morphine was only injected. It is worth noting that 30 min before the morning dose of morphine, duloxetine (10, 20, and 40 mg/kg) was injected intraperitoneally. In addition, 2 h after the last injection of morphine, the morphine withdrawal was precipitated by naloxone. The withdrawal signs were recorded for 30 min; these signs included jumping, rearing, genital grooming, abdominal writhing, wet dog shaking, and teeth grinding.

Results:

The results of the study revealed that the chronic administration of duloxetine decreased all the withdrawal signs. Besides, it attenuated the total withdrawal scores significantly.

Conclusion:

Results indicate that the regulatory effects on serotonergic and noradrenergic parameters might be associated with the amelioration of the withdrawal symptoms.

Key words

duloxetine - morphine - withdrawal syndrome - rat - serotonin
 

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