Ethanol intake and ethanol-conditioned place preference are reduced in mice treated with the bioflavonoid agent naringin

Amine Bahi, Syed M. Nurulain, Shreesh Ojha

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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 (10-100mg/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 [15-60μM (w/v)] intake. In addition, there was no significant difference in blood ethanol concentration (BEC) between groups following naringin administration of 3g of ethanol/kg body weight. Interestingly, when mice were treated with vehicle or naringin (30mg/kg) before injection of ethanol (1.5g/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.

Original languageEnglish
Pages (from-to)677-685
Number of pages9
JournalAlcohol
Volume48
Issue number7
DOIs
Publication statusPublished - Nov 1 2014

Keywords

  • CPP
  • Conditioned place preference
  • Ethanol
  • GW9662
  • NAChRs
  • NAR
  • Naringin
  • PPAR
  • Peroxisome proliferator-activated receptors
  • TZD
  • Two-bottle choice

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

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