Excessive high fat diet (HFD) consumption can induce food addiction, which is believed to involve the communication between the hypothalamus and mesolimbic dopaminergic neurons, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc). These brain areas are densely populated with opioid receptors, raising the possibility that these receptors, and particularly mu opioid receptors (MORs), are involved in rewards elicited by palatable food. This study sought to investigate the involvement of MORs in HFD-induced reward and if there is any difference between male and female subjects in this response. We also assessed if exposure to HFD would alter the rewarding action of oxycodone, a relatively selective MOR agonist. The place conditioning paradigm was used as an animal model of reward to determine if short-time (STC, 2 h) or long-time (LTC, 16 h) conditioning with HFD induces reward or alters the rewarding action of oxycodone. Male and female C57BL/6J mice as well as MOR knockout and their wildtype littermates of both sexes were tested for basal place preference on day 1 and then conditioned with an HFD in one chamber and a regular chow diet (RCD) in another chamber for 2 h on alternate days. Three sets of STC were used, followed by a set of LTC. Each set of conditioning consisted of two conditioning with RCD and two conditioning with HFD. Mice were tested for place preference after each set of STC and again after LTC. Controls were conditioned with RCD in both conditioning chambers. Following the last place preference test, mice were treated with oxycodone and conditioned in the HFD-paired chamber and with saline in the RCD-paired chamber for one hour once a day to explore the possibility if the HFD could alter oxycodone reward. The result showed that HFD induced conditioned place preference (CPP) in male but not female subjects. However, oxycodone conditioning elicited reward in both male and female mice of the HFD group but not the control group, showing that prior conditioning with HFD potentiated the rewarding action of oxycodone. The latter response was mediated via MORs, as it was blunted in MOR knockout mice. Similarly, HFD-induced CPP was blunted in male MOR knockout mice, suggesting sexual dimorphism in this response. Full article

Background: Cancer is, at present, among the leading causes of morbidity globally. Despite advances in treatment regimens for cancer, patients suffer from poor prognoses. In this context, the availability of vast natural resources seems to alleviate the shortcomings of cancer chemotherapy. The last decade has seen a breakthrough in the investigations related to the anticancer potential of dietary phytoconstituents. Interestingly, a handsome number of bioactive principles, ranging from phenolic acids, phenylpropanoids, flavonoids, stilbenes, and terpenoids to organosulphur compounds have been screened for their anticancer properties. Among the phenylpropanoids currently under clinical studies for anticancer activity, eugenol is a promising candidate. Eugenol is effective against cancers like breast, cervical, lung, prostate, melanomas, leukemias, osteosarcomas, gliomas, etc., as evident from preclinical investigations. Objective: The review aims to focus on cellular and molecular mechanisms of eugenol for cancer prevention and therapy. Methods: Based on predetermined criteria, various scholarly repositories, including PubMed, Scopus, and Science Direct were analyzed for anticancer activities of eugenol. Results: Different biochemical investigations reveal eugenol inducing cytotoxicity, inhibiting phases of the cell cycles, programmed cell death, and auto-phagocytosis in studied cancer lines; thus, portraying eugenol as a promising anticancer molecule. A survey of current literature has unveiled the molecular mechanisms intervened by eugenol in exercising its anticancer role. Conclusion: Based on the critical analysis of the literature, eugenol exhibits vivid signaling pathways to combat cancers of different origins. The reports also depict the advancement of novel nano-drug delivery approaches upgrading the therapeutic profile of eugenol. Therefore, eugenol nanoformulations may have enormous potential for both the treatment and prevention of cancer. Full article