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 AffiliationsFunding: 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.
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
2
Ghavimi H,
Darvishi S,
Ghanbarzadeh S.
Attenuation of morphine-induced tolerance and dependence by pretreatment with
cerebrolysin in male rats. Drug Res 2018; 68: 33-37
3
Alavi MS,
Hosseinzadeh H,
Shamsizadeh A.
et al. The effect of O-1602, an atypical cannabinoid, on morphine-induced conditioned
place preference and physical dependence. Pharmacol Rep 2016; 68: 592-597
10
Liang J,
Cagetti E,
Olsen RW.
et al. Altered pharmacology of synaptic and extrasynaptic GABAA receptors on CA1
hippocampal neurons is consistent with subunit changes in a model of alcohol
withdrawal and dependence. J Pharmacol Exp Ther 2004; 310: 1234-1245
11
Liang J,
Lopez-Valdes HE,
Martinez-Coria H.
et al. Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of
transgenic mouse models of Alzheimer’s disease. Neurochem Res 2014; 39: 1171-1181
12
Rezayof A,
Razavi S,
Haeri-Rohani A.
et al. GABA(A) receptors of hippocampal CA1 regions are involved in the acquisition and
expression of morphine-induced place preference. Eur Neuropsychopharmacol 2007; 17: 24-31
13
Cabral A,
Ruggiero RN,
Nobre MJ.
et al. GABA and opioid mechanisms of the central amygdala underlie the
withdrawal-potentiated startle from acute morphine. Prog Neuro-psychopharmacol 2009; 33: 334-344
16
Li Y,
Li GY,
Li LJ.
et al. Subsequently enhanced CPP to morphine following chronic but not acute footshock
stress associated with corticosterone mechanism in rats. Int J Neurosci 2007; 117: 1237-1255
17
Parvardeh S,
Moghimi M,
Eslami P.
et al. α-Terpineol attenuates morphine-induced physical dependence and
tolerance in mice: Role of nitric oxide. Iran J Basic Med Sci 2016; 19: 201-208
18
Park SW,
Roohbakhsh A,
Beninger RJ.
8-pCPT, an Epac activator, impairs conditioned place preference based on nucleus
accumbens amphetamine in rats. Acta neuropsychiatr 2014; 26: 104-111
19
Zarrindast MR,
Mohajeri S.
Influence of ATP-dependent K+ channels on nicotine-induced inhibition of
withdrawal in morphine-dependent mice. Eur J Pharmacol 2006; 552: 90-98
21
Liu L,
Wan J,
Lang H.
et al. Dihydromyricetin delays the onset of hyperglycemia and ameliorates insulin
resistance without excessive weight gain in Zucker diabetic fatty rats. Mol Cell Endocrinol 2017; 439: 105-115
22
Ren ZX,
Zhao YF,
Cao T.
et al. Dihydromyricetin protects neurons in an MPTP-induced model of
Parkinson’s disease by suppressing glycogen synthase kinase-3 beta
activity. Acta Pharm Sinic 2016; 37: 1315-1324
23
Ren Z,
Yan P,
Zhu L.
et al. Dihydromyricetin exerts a rapid antidepressant-like effect in association with
enhancement of BDNF expression and inhibition of neuroinflammation. Psychopharmacol 2018; 235: 233-244
24
Ling H,
Zhu Z,
Yang J.
et al. Dihydromyricetin improves type 2 diabetes-induced cognitive impairment via
suppressing oxidative stress and enhancing brain-derived neurotrophic
factor-mediated neuroprotection in mice. Acta Bioch Bioph Sin 2018; 50: 298-306
25
Cai Y,
Yang L,
Hu G.
et al. Regulation of morphine-induced synaptic alterations: Role of oxidative stress,
ER stress, and autophagy. J Cell Biol 2016; 215: 245-258
26
Yang W,
He H,
Pan Y.
et al. Cocaine withdrawal reduces Gamma-Aminobutyric Acid-Ergic transmission and
gephyrin expression at medial prefrontal cortex in cocaine-conditioned
place-preference rats, which shows increased cocaine seeking. Eur addict Res 2017; 23: 28-36
27
Zarrindast MR,
Ahmadi S,
Haeri-Rohani A.
et al. GABA(A) receptors in the basolateral amygdala are involved in mediating morphine
reward. Brain Res 2004; 1006: 49-58
28
McKernan RM,
Rosahl TW,
Reynolds DS.
et al. Sedative but not anxiolytic properties of benzodiazepines are mediated by the
GABA(A) receptor alpha1 subtype. Nat Neurosci 2000; 3: 587-592
29
Sieghart W,
Savić MM.
International Union of Basic and Clinical Pharmacology. CVI: GABA(A) Receptor
Subtype- and Function-selective Ligands: Key Issues in Translation to
Humans. Pharmacol Rev 2018; 70: 836-878
30
Atack JR.
GABAA receptor subtype-selective modulators. I.
α2/α3-selective agonists as non-sedating
anxiolytics. Curr Top Med Chem 2011; 11: 1176-1202
31
Atack JR,
Wafford KA,
Tye SJ.
et al. TPA023
[7-(1,1-dimethylethyl)-6-(2-ethyl-2H-1,2,4-triazol-3-ylmethoxy)-3-(2-fluorophenyl)-1,2,4-triazolo[4,3-b]pyridazine],
an agonist selective for alpha2- and alpha3-containing GABAA receptors, is a
nonsedating anxiolytic in rodents and primates. J Pharmacol Exp Ther 2006; 316: 410-422
32
Morales M,
Varlinskaya EI,
Spear LP.
Anxiolytic effects of the GABA(A) receptor partial agonist, L-838,417: impact of
age, test context familiarity, and stress. Pharmacol, Biochem, Behav 2013; 109: 31-37
33
Liang J,
López-Valdés HE,
Martínez-Coria H.
et al. Dihydromyricetin ameliorates behavioral deficits and reverses neuropathology of
transgenic mouse models of Alzheimer’s disease. Neurochem Res 2014; 39: 1171-1181
34
Wang L,
Li BR,
Xiao ZY.
et al. Dihydromyricetin ameliorates chronic social defeat stress induced cognitive and
affective disorder in mice. Chinese J Physiol 2019; 35: 496-500
36
Naidu PS,
Singh A,
Joshi D.
et al. Possible mechanisms of action in quercetin reversal of morphine tolerance and
dependence. Addict Biol 2003; 8: 327-336
39
Chen S,
Zhao X,
Wan J.
et al. Dihydromyricetin improves glucose and lipid metabolism and exerts
anti-inflammatory effects in nonalcoholic fatty liver disease: A randomized
controlled trial. Pharmacol Res 2015; 99: 74-81