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Drug Res (Stuttg) 2020; 70(09): 410-416
DOI: 10.1055/a-1206-6757
Original Article

The Effect of Dihydromyricetin, a Natural Flavonoid, on Morphine-induced Conditioned Place Preference and Physical Dependence in Mice

Leila Etemad
1   Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
,
Hadi Farkhari
2   Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
,
Mohaddeseh Sadat Alavi
3   Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
4   Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
,
Ali Roohbakhsh
1   Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
› Author Affiliations Funding: This paper is extracted from a Pharm.D. thesis and was supported by a grant (no. 931672) from the Research Council of Mashhad University of Medical Sciences, Mashhad University of Medical Sciences.
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Abstract

Objective Dihydromyricetin (DHM), a natural flavonoid, is used to reduce alcohol hangover. It has a modulatory role on GABAA receptors with significant effects on seizure and anxiety in animal models. We aimed to evaluate the effect of DHM on morphine conditioned place preference (CPP) and withdrawal sings following morphine dependence using animal models.

Methods The effect of DHM (1, 2 and 5 mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP was evaluated in male mice. Administration of morphine for three consecutive days induced physical dependence. The withdrawal signs such as jumping and defecation were precipitated by administration of naloxone (8 mg/kg, ip). The effect of DHM on the development of physical dependence was assessed by injection of DHM before morphine administrations.

Results DHM, at the dose of 5 mg/kg, reduced expression of morphine CPP with an increase in the locomotor activity. DHM, at the doses of 2 and 5 mg/kg, also reduced development of morphine CPP. DHM alleviated development of morphine-induced physical dependence at the dose of 1, 2, and 5 mg/kg by decreasing jumping and defecation.

Conclusion These results indicated that DHM decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.

Key words

drug dependence - analgesic drugs - behavioural pharmacology - drugs of abuse


Publication History

Received: 08 April 2020

Accepted: 22 June 2020

Article published online:
17 July 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

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