Effects of consuming a diet high in fat and/or sugar on the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice

Drug abuse and obesity are serious public health problems. Dopamine plays a central role in mediating the reinforcing effects of drugs and food. Prolonged use of drugs is known to alter the function and/or sensitivity of many neurotransmitter systems, including dopamine, however, the impact of consuming foods high in fat and/or sugar is less clear. These studies characterized the locomotor effects of acute and repeated cocaine in male and female C57BL/6J mice consuming 1 of 4 diets: (a) standard chow + water; (b) standard chow + 10% sucrose solution; (c) high-fat chow + water; or (d) high-fat chow + 10% sucrose solution. The acute locomotor effects of cocaine (3.2-32.0 mg/kg) were evaluated 4 weeks after initiating dietary conditions; the effects of repeated cocaine administration were evaluated after 5, 6, 7, and 12 weeks. During acute tests, mice consuming a diet high in fat and/or sucrose exhibited greater locomotor responses to cocaine than mice consuming standard chow and water, regardless of sex. Although diet-induced enhancements persisted across repeated cocaine testing, locomotor sensitization developed more rapidly in females drinking sucrose (and consuming either standard or high-fat chow) than in females consuming standard chow and water. In addition to providing evidence that consuming a diet high in fat and/or sugar enhances abuse-related effects of cocaine in ways that might increase vulnerability to abuse cocaine, these studies identified a potentially important sex-related difference in the interaction between nutrition and cocaine effects, with the impacts of sucrose consumption being greater in females than in males.