Effects of junk-food on food-motivated behavior and NAc glutamate plasticity; insights into the mechanism of NAc calcium-permeable AMPA receptor recruitment

In rats, eating obesogenic diets increase calcium-permeable AMPA receptor (CP-AMPAR) transmission in the nucleus accumbens (NAc) core, and enhances food-motivated behavior. Interestingly these diet-induced alterations in NAc transmission are pronounced in obesity-prone (OP) rats and absent in obesity-resistant (OR) populations. However, effects of diet manipulation on food motivation, and the mechanisms underlying NAc plasticity in OPs is unknown. Using male selectively-bred OP and OR rats, we assessed food-motivated behavior following ad lib access to chow (CH), junk-food (JF), or 10d of JF followed by a return to chow diet (JF-Dep). Behavioral tests included conditioned reinforcement, instrumental responding, and free consumption. Additionally, optogenetic, chemogenetic, and pharmacological approaches were used to examine NAc CP-AMPAR recruitment following diet manipulation and ex vivo treatment of brain slices. Motivation for food was greater in OP than OR rats, as expected. However, JF-Dep only produced enhancements in food-seeking in OP groups, while continuous JF access reduced food-seeking in both OPs and ORs. Reducing excitatory transmission in the NAc was sufficient to recruit CP-AMPARs to synapses in OPs, but not ORs. In OPs, JF-induced increases in CP-AMPARs occurred in mPFC-, but not BLA-to-NAc inputs. Diet differentially affects behavioral and neural plasticity in obesity susceptible populations. We also identify conditions for acute recruitment of NAc CP-AMPARs; these results suggest that synaptic scaling mechanisms contribute to NAc CP-AMPAR recruitment. Overall, this work improves our understanding of how sugary, fatty food consumption interacts with obesity susceptibility to influence food-motivated behavior. It also extends our fundamental understanding of NAc CP-AMPAR recruitment; this has important implications for motivation in the context of obesity as well as drug addiction.