Blocking the increased reinforcing effects of cocaine induced by social defeat: Effects of palatable food

Preclinical studies suggest that stimulation of the brain's reward system by high-fat diets (HFD) could act as an alternative reinforcer. The main aim of the present study was to evaluate the effect of a limited and intermittent exposure to an HFD administered during and after exposure to Social Defeat (SD) on a non-effective dose of cocaine-induced Conditioned Place Preference (CPP). Experiment 1 consisted of modulating SD episodes with three different patterns of HFD access: 1h access before each session of SD; 2h access three days a week during the two weeks of SD exposure; and 2h access 4h after each SD. Experiment 2 consisted of modulating the effects of stress on CPP acquisition with three patterns of HFD access: 1h access before each conditioning session; 2h access three days a week throughout the two-week period of the CPP; and 2h access three days a week from the last SD episode to the end of CPP. HFD administered during the period of SD episodes counteracted the increased sensitivity that SD produces on the reinforcing effects of cocaine. Access to HFD before the conditioning session or three days a week (CPP-SD-MWF) during the acquisition of CPP blocked this increased sensitivity. In the striatum, SD induced a decrease in the cannabinoid 1 receptor (Cb1r) gene expression, not affected by HFD, and increased corticotrophin releasing hormone receptor 1 (Crhr1) gene expression, except for those mice fed on HFD after SD encounters. Our findings indicate that a small intake of HFD may attenuate the social stress-induced increase in the rewarding properties of cocaine.