Structural and Functional Plasticity within the Nucleus Accumbens and Prefrontal Cortex Associated with Time-Dependent Increases in Food Cue-Seeking Behavior

Abstract

Urges to consume food can be driven by stimuli in the environment that are associated with previous food experience. Identifying adaptations within brain reward circuits that facilitate cue-induced food seeking is critical for understanding and preventing the overconsumption of food and subsequent weight gain. Utilizing electrophysiological, biochemical, and DiI labeling, we examined functional and structural changes in the nucleus accumbens (NAc) and prefrontal cortex (PFC) associated with time-dependent increases in food craving ('incubation of craving'). Rats self-administered 60% high fat or chow 45 mg pellets and were then tested for incubation of craving either 1 or 30 days after training. High fat was chosen for comparison to determine whether palatability differentially affected incubation and/or plasticity. Rats showed robust incubation of craving for both food rewards, although responding for cues previously associated with high fat was greater than chow at both 1 and 30 days. In addition, previous experience with high-fat consumption reduced dendritic spine density in the PFC at both time points. In contrast, incubation was associated with an increase in NAc spine density and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated transmission at 30 days in both groups. Finally, incubation of craving for chow and high fat was accompanied by an increase in calcium-permeable and calcium-impermeable AMPARs, respectively. Our results suggest that incubation of food craving alters brain reward circuitry and macronutrient composition specifically induces cortical changes in a way that may facilitate maladaptive food-seeking behaviors.

Central nucleus of the amygdala as a common substrate of the incubation of drug and natural reinforcer seeking

“…For example, after cocaine seeking incubation, there is an increase of CP‐AMPAR‐mediated synapses in both the core and shell subregions, although the source of these synapses in the core is not clear . Interestingly, while after the incubation of food seeking there is an increase of AMPA/NMDA ratio in the core, a decrease of this ratio is evident in after the incubation of sucrose seeking . We have detected some changes of similar nature but more likely due to the self‐administration of the different substances (a reduction of Gria2 , expression in the core 24 hours after the last session of sucrose self‐administration, or increases in the expression of Gria1 , and the Gria1/Gria2 ratio in the shell after heroin or cocaine self‐administration, respectively; see Data S1).…”

Incubation of food craving in rats: A review

“…Related to the findings with DARPP32, other laboratories have reported plasticityrelated changes correlating with incubation of food craving. Specifically, incubation of sucrose craving was associated with a decreased glutamate AMPA/NMDA receptor ratio in the nucleus accumbens (a mesolimbic dopamine terminal region, noted above; Counotte, Schiefer, Shaham, & O'Donnell, 2014), while incubation of standard or high-fat pellet craving was associated with food-type specific changes in nucleus accumbens dendritic spine density and AMPA receptors (Dingess et al, 2017).…”

“…Specifically, incubation of sucrose craving was associated with a decreased glutamate AMPA/NMDA receptor ratio in the nucleus accumbens (a mesolimbic dopamine terminal region, noted above; Counotte, Schiefer, Shaham, & O'Donnell, 2014), while incubation of standard or high-fat pellet craving was associated with food-type specific changes in nucleus accumbens dendritic spine density and AMPA receptors (Dingess et al, 2017). Specifically, incubation of sucrose craving was associated with a decreased glutamate AMPA/NMDA receptor ratio in the nucleus accumbens (a mesolimbic dopamine terminal region, noted above; Counotte, Schiefer, Shaham, & O'Donnell, 2014), while incubation of standard or high-fat pellet craving was associated with food-type specific changes in nucleus accumbens dendritic spine density and AMPA receptors (Dingess et al, 2017).…”

“…Rats responded in ten 6-hr daily sessions for intravenous cocaine and a tone+light cue. examined incubation of craving for complex foods and fats (e.g., standard or high-fat food pellets; Darling et al, 2016;Dingess et al, 2017;McCue, Kasper, & Hommel, 2019). * Indicates significant difference from Day 1, p < .05.…”

“…Copyright 2003 by the Society for Neuroscience. examined incubation of craving for complex foods and fats (e.g., standard or high-fat food pellets; Darling et al, 2016;Dingess et al, 2017;McCue, Kasper, & Hommel, 2019). An exhaustive review of the incubation literature reveals studies of incubation of drug craving that include incubation of food craving as a comparison condition.…”