title: Ethanol intake and ethanol-conditioned place preference are reduced in mice treated with the bioflavonoid agent naringin.
abstract: Recently, PPAR-γ activation has emerged as a potential treatment for alcoholism. However, the adverse effects of synthetic PPAR-γ activators, despite being effective drugs, prompted the need for novel PPAR-γ agonists that retain efficacy and potency with a lower potential of side effects. Hence, naringin, a bioflavonoid isolated from citrus fruits and recently identified as a natural ligand of PPAR-γ, has begun to be evaluated for treatment of alcoholism. It is well known to possess several therapeutic benefits in addition to its anti-anxiety and antidepressant properties. In the present study, we assessed whether naringin treatment possesses anti-ethanol reward properties in C57BL/6 mice. We used the two-bottle choice drinking paradigm and ethanol-induced conditioned place preference (CPP) to examine the effect of naringin treatment on ethanol drinking. Results have shown that, compared with vehicle, naringin (10-100 mg/kg) significantly and dose-dependently decreased voluntary ethanol intake and preference in a two-bottle choice drinking paradigm [3-15% (v/v) escalating over 2 weeks], with no significant effect observed on saccharin [0.02-0.08% (w/v)] or on quinine [15-60 μM (w/v)] intake. In addition, there was no significant difference in blood ethanol concentration (BEC) between groups following naringin administration of 3 g of ethanol/kg body weight. Interestingly, when mice were treated with vehicle or naringin (30 mg/kg) before injection of ethanol (1.5 g/kg) during conditioning days, naringin inhibited the acquisition of ethanol-CPP. More importantly, these effects were significantly attenuated when mice were pre-injected with the peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist, GW9662. Taken together, the present findings are the first to implicate naringin and PPAR-γ receptors in the behavioral and reward-related effects of ethanol and raise the question of whether specific drugs that target PPAR-γ receptors could potentially reduce excessive ethanol consumption and preference.
authors.affiliation: Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, United Arab Emirates. Electronic address: amine.bahi@uaeu.ac.ae.
authors.forename: Amine
authors.initials: A
authors.lastname: Bahi
authors.affiliation: Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Syed M
authors.initials: SM
authors.lastname: Nurulain
authors.affiliation: Department of Pharmacology & Therapeutics, College of Medicine & Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
authors.forename: Shreesh
authors.initials: S
authors.lastname: Ojha
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000523:psychology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects; D044950:Flavanones / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D005419:Flavonoids / Q000037:antagonists & inhibitors / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D012201:Reward; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D044950:Flavanones; D005419:Flavonoids; D047495:PPAR gamma; C005274:naringin
keywords: Conditioned place preference; Ethanol; GW9662; Naringin; Peroxisome proliferator-activated receptors; Two-bottle choice