Grape Seed Proanthocyanidins Attenuate Anxiety-Like Behavior in an Experimental Model of Dietary-Induced Hypercholesterolemia in Rats

Abstract. Objective: Grape seed proanthocyanidins have many health-protective effects. The present work aimed to assess their possible anxiolytic effects in dietary-induced hypercholesterolemia in rats. Methods: 30 Male Wistar rats were divided into 3 groups (n = 10): control (normal chow), high cholesterol (cholesterol and cholic acid chow) and high cholesterol + grape seed extract (hypercholesterolemic chow + grape seed extract, 100 mg/kg body weight/day). After 4 months, total cholesterol levels and animals’ behavior in the open field and elevated plus maze were assessed. Results: High-cholesterol diet elevated cholesterol levels (p < 0.001 vs control group), however, grape seed administration ameliorated this elevation (p < 0.001 vs high-cholesterol untreated group). In the open field, hypercholesterolemic rats showed increased periods of immobility (138 ± 20.3 seconds (s) vs 96.9 ± 14.5 in control rats p < 0.001) and time latency to enter field center (109 ± 18.3 s compared to 40.8 ± 10.5 s in the control group p < 0.001). Both parameters were reduced by grape seed treatment (p < 0.01, p < 0.001 vs the untreated hypercholesterolemic group, respectively). Elevated plus maze testing demonstrated higher closed-arm entries (5.5 ± 1.1 in hypercholesterolemic animals vs 3 ± 1.1 in the control group p < 0.001) and lower percentage of time spent in open arms (19.7 ± 3.5 % vs 35.8 ± 4.8 % in control rats p < 0.001). Grape seed extract significantly enhanced the percentage of time spent in open arms (p < 0.001 compared to hypercholesterolemic rats). Conclusion: The present results highlight the possible anxiolytic effect of grape seed proanthocyanidins in dietary-induced hypercholesterolemia.