Incubation of palatable food craving is associated with brain-wide neuronal activation in mice

Hot Off the Press – November 21, 2022

Summary

Relapse to reward seeking progressively increases during abstinence, a behavioral phenomenon termed incubation of craving. Mechanistic studies of incubation can lead to novel relapse treatments. However, previous studies have primarily used rat models and targeted region-by-region analyses, and a brain-wide functional atlas of incubation of reward seeking is lacking. We established a behavioral procedure for incubation of palatable food seeking in mice and applied whole-brain activity mapping with Fos as a neuronal activity marker to identify the functional connectome of this incubation. Like rats, mice showed incubation of food seeking during abstinence. Using two complementary activity mapping approaches, we identified a brain-wide pattern of increased neural activation that mirrored incubation of food seeking after 60, but not 1 or 15 abstinence days.

Publication Information

Madangopal, Rajtarun; Szelenyi, Eric R.; Nguyen, Joseph; Brenner, Megan B.; Drake, Olivia R.; Pham, Diana Q.; Shekara, Aniruddha; Jin, Michelle; Choong, Jia Jie; Heins, Conor; Komer, Lauren E.; Weber, Sophia J.; Hope, Bruce T.; Shaham, Yavin; Golden, Sam A.

Incubation of palatable food craving is associated with brain-wide neuronal activation in mice Journal Article

In: Proceedings of the National Academy of Sciences, vol. 119, no. 45, pp. e2209382119, 2022.

Abstract | Links

@article{doi:10.1073/pnas.2209382119,

title = {Incubation of palatable food craving is associated with brain-wide neuronal activation in mice},

author = {Rajtarun Madangopal and Eric R. Szelenyi and Joseph Nguyen and Megan B. Brenner and Olivia R. Drake and Diana Q. Pham and Aniruddha Shekara and Michelle Jin and Jia Jie Choong and Conor Heins and Lauren E. Komer and Sophia J. Weber and Bruce T. Hope and Yavin Shaham and Sam A. Golden},

url = {https://www.pnas.org/doi/abs/10.1073/pnas.2209382119},

doi = {10.1073/pnas.2209382119},

year  = {2022},

date = {2022-01-01},

journal = {Proceedings of the National Academy of Sciences},

volume = {119},

number = {45},

pages = {e2209382119},

abstract = {Studies using rodent models have shown that relapse to drug or food seeking increases progressively during abstinence, a behavioral phenomenon termed ``incubation of craving.'' Mechanistic studies of incubation of craving have focused on specific neurobiological targets within preselected brain areas. Recent methodological advances in whole-brain immunohistochemistry, clearing, and imaging now allow unbiased brain-wide cellular resolution mapping of regions and circuits engaged during learned behaviors. However, these whole-brain imaging approaches were developed for mouse brains, while incubation of drug craving has primarily been studied in rats, and incubation of food craving has not been demonstrated in mice. Here, we established a mouse model of incubation of palatable food craving and examined food reward seeking after 1, 15, and 60 abstinence days. We then used the neuronal activity marker Fos with intact-brain mapping procedures to identify corresponding patterns of brain-wide activation. Relapse to food seeking was significantly higher after 60 abstinence days than after 1 or 15 days. Using unbiased ClearMap analysis, we identified increased activation of multiple brain regions, particularly corticostriatal structures, following 60 but not 1 or 15 abstinence days. We used orthogonal SMART2 analysis to confirm these findings within corticostriatal and thalamocortical subvolumes and applied expert-guided registration to investigate subdivision and layer-specific activation patterns. Overall, we 1) identified brain-wide activity patterns during incubation of food seeking using complementary analytical approaches and 2) provide a single-cell resolution whole-brain atlas that can be used to identify functional networks and global architecture underlying the incubation of food craving.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}