191 - Effectiveness of an imagery-replacement strategy on the intensity of food cravings

Abstract

Introduction: Cognitive and behavioural responses to food reward are associated with individual differences in reward-responsiveness and impulsivity. There is evidence for decision-making deficits in individuals with obesity and binge-eating disorder. Despite these data, there is a lack of understanding about neural mechanisms contributing to altered motivation and impulsivity for food. Dopamine (DA) neurons in the ventral tegmental area (VTA) of the midbrain and their limbic targets in the nucleus accumbens (NAc) and dorsal striatum (DS), are an essential component of the neural circuitry underlying motivation and reward. Methods: To examine the molecular adaptations in reward circuitry to a high-fat and sugar diet (HFD), male C57Bl6 mice were placed on a HFD or control low-fat diet (LFD) for 12 weeks. Protein from NAc, DS and VTA microdissections was subject to immunoblotting using antibodies against D1 receptor, D2 receptor, brain-derived neurotrophic factor (BDNF), phospho-DARPP-32, phospho-CREB, and ΔFosB. results: Most notably, HFD mice had significantly higher D2R, BDNF, and ΔFosB in the NAc, as compared to LFD mice and D2R and ΔFosB levels strongly correlated with weight gain. Intriguingly, increases in BDNF and ΔFosB in the NAc are associated with enhanced sensitivity to the rewarding effects of cocaine. Here we also show that the rewarding effects of high-fat food and food impulsivity can be measured in mice using progressive ratio and delay discounting tasks, respectively. We are currently using these behavioural measures to assess changes in food reward and impulsivity in mice following acute or chronic HFD or LFD. conclusions: Teasing apart the pathways and signaling molecules that underlie motivation for food remains a very important goal pertinent to a major national health issue.