TY - JOUR
T1 - Ethanol intake and ethanol-conditioned place preference are reduced in mice treated with the bioflavonoid agent naringin
AU - Bahi, Amine
AU - Nurulain, Syed M.
AU - Ojha, Shreesh
N1 - Funding Information:
Role of the funding source: The research grant support from the United Arab Emirates University and the National Research foundation, UAE to AB (grant No. 31M082 ) and SO (grant No. 31M099 ) are duly acknowledged. The funders had no further role in study design, in the collection, analysis and interpretation of data, in the writing of the report, and in the decision to submit the paper for publication.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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.
AB - 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.
KW - CPP
KW - Conditioned place preference
KW - Ethanol
KW - GW9662
KW - NAChRs
KW - NAR
KW - Naringin
KW - PPAR
KW - Peroxisome proliferator-activated receptors
KW - TZD
KW - Two-bottle choice
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U2 - 10.1016/j.alcohol.2014.06.008
DO - 10.1016/j.alcohol.2014.06.008
M3 - Article
C2 - 25288222
AN - SCOPUS:84908018357
SN - 0741-8329
VL - 48
SP - 677
EP - 685
JO - Alcohol
JF - Alcohol
IS - 7
ER -