Anecdotic evidence suggests fruit ingestion may be followed by an inner sensation of wellbeing, but biological basis for this phenomenon is not fully explained. Our aim was to investigate if there was a plausible biological mechanism that could explain if ingestion of fruit bioactives (polyphenols) could make us “feel good”. NS20Y (ATCC 08062517) cells were cultured according to procedures and increasing concentrations of FruitOx (proprietary fruit-polyphenols blend extract) added to the media. Viability at 24h using Presto BlueTM showed no statistically significant differences at increasing concentrations (0-50 ppm). Quantitative real-time RT-PCR analysis showed slight (1.5) but statistically significant (p<0.009) upregulation of delta opioid receptor 1 (OPRD1). Quantification of the protein by the fluorometric method showed no statistically significant difference between FruitOx treated and control cells. In silico evaluation of the bioactives contained in the fruit blend revealed that Chlorogenic acid (polar surface area 164, predicted bioactivity: G-coupled protein receptor, nuclear receptor) was the most likely candidate for eliciting such effect, suggesting a biological plausibility. We conclude that bioactive substances in fruits maybe able to stimulate neural pathways that may reinforce healthy eating habits. Further in vivo work is necessary to validate this theory.