Incubation of food craving in rats: A review

Abstract

Incubation of food craving is an abstinence-dependent increase in responding for reward-paired cues. Incubation of craving was first reported for rats responding for cocaine-paired cues, and later generalized to several drugs of abuse and for food. Incubation of drug and food craving has been reported in clinical studies as well. Incubation of food craving by rats has been reported for standard chow as well as for high fat and sucrose reinforcers. Parametric and other evaluations of the incubation of food craving reveal manipulations that reduce incubation, including environmental enrichment and pharmacological manipulation of dopamine, glutamate, and endogenous opiates. Several brain regions are likely involved in the effect, including mesolimbic terminals and the central nucleus of the amygdala. Further study of the incubation of food craving could facilitate development of treatments for cravings that precede relapse characteristic of drug and food addictions.

Keywords: abstinence; addiction; craving; drug; food; incubation; relapse.

Fig. 1.

Incubation of cocaine craving in rats. Rats responded in ten 6-hr daily sessions for intravenous cocaine and a tone+light cue. After increasing days of abstinence (withdrawal) rats responded in six 1-hr extinction sessions without the cue (top panel) and a subsequent 1-hr session with response-contingent cue delivery (bottom panel). * Indicates significant difference from Day 1, p < .05. Adapted from Grimm et al., 2001. Copyright 2001 by Springer Nature.

Fig. 2.

Incubation of sucrose craving in rats. Rats responded in ten 6-hr daily sessions for a liquid drop of sucrose and a tone+light cue. After 1, 30, or 90 days of abstinence (withdrawal) rats responded in six 1-hr extinction sessions without the cue (not shown here) and a subsequent 1-hr session with response-contingent cue delivery (Figure). * Indicates significant difference from Day 1, p < .05. Adapted from “Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: implications for incubation of cocaine craving,” by Grimm et al. (2003). Copyright 2003 by the Society for Neuroscience.

Fig. 3.

General Method. Adapted from “Brief exposure to novel or enriched environments reduces sucrose cue-reactivity and consumption in rats after 1 or 30 days of forced abstinence from self-administration,” by Grimm et al., 2013. Copyright 2013 by the authors.

Fig. 4.

Incubation of sucrose taking in rats. Rats responded in ten 2-hr daily sessions for a liquid drop of sucrose and a tone+light cue. After 1 or 30 days of abstinence rats responded in a 2-hr extinction session with the cue (not shown here). The next day rats responded in a 2-hr session with the same reinforcement contingencies as during training. * Indicates significant difference from Day 1, p < .05. Adapted from Grimm et al., 2013. Copyright 2013 by the authors.

Fig. 5.

Incubation of sucrose craving is not attenuated by sucrose satiation. Rats responded in ten 6-hr daily sessions for a liquid drop of sucrose and a tone+light cue. Either the afternoon of the 10^th day of training, or 29 days later, rats were provided a bottle of 10% sucrose in the home cage until immediately before cue-reactivity testing the next day. During the next day testing, rats responded in six 1-hr extinction sessions without the cue (not shown here) and a subsequent 1-hr session with response-contingent cue delivery (Figure). * Indicates significant difference from Day 1, p < .05. Adapted from Grimm et al., 2005. Copyright 2004 by Elsevier Inc. Reprinted with permission.

Fig. 6.

Incubation of sucrose craving is attenuated by recent devaluation of sucrose with LiCl. Rats responded in ten 2-hr daily sessions for a liquid drop of sucrose and a tone+light cue. Either the next 3 days, or days 31–33 of abstinence, sucrose was paired with LiCl in a novel environment. The next day rats were tested for sucrose cue-reactivity by allowing them to respond in extinction conditions including the tone+light cue. # Indicates significant difference from Day 1 Saline control, * indicates significant difference from Day 30 Saline control, p’s < .05. Adapted from Harkness et al., 2010. Copyright 2009 by Springer-Verlag. Reprinted with permission.

Fig. 7.

Incubation of sucrose craving is attenuated by Environmental Enrichment. Rats responded in ten 2-hr daily sessions for a liquid drop of sucrose and a tone+light cue. For acute EE, rats were placed into EE the afternoon of the 10^th day of training or the afternoon of the 29^th day of abstinence. Testing occurred the next day (Day 1 or Day 30 of abstinence). For chronic EE, rats were placed into EE from the afternoon of the 10^th day of training until testing on Day 30 of abstinence. Rats were tested for sucrose cue-reactivity by allowing them to respond in extinction conditions including the tone+light cue. Control (CON) Day 30 was significantly greater than CON Day 1 responding (not shown on Figure). Data in this figure have been transformed to represent percent of the Day 1 abstinence control average responding. *Indicates significant difference from CON Day 30, X indicates significant difference from EE Acute Day 1, p’s < .05. Adapted from Grimm et al., 2013. Copyright 2013 by the authors.

Fig. 8.

Incubation of sucrose craving is attenuated by a dopamine D1 receptor antagonist. Rats responded in ten 2-hr daily sessions for a liquid drop of sucrose and a tone +light cue. Rats were tested for sucrose cue-reactivity by allowing them to respond in extinction conditions including the tone+light cue either 1 or 30 days into sucrose abstinence. Fifteen minutes before testing, rats were injected with saline or one of three doses of SCH23390. * Indicates significant difference from saline on that day of abstinence, † indicates significant difference from Day 1 at that dose, p’s < .05. Adapted from Grimm et al., 2011. Copyright 2011 by Springer-Verlag. Reprinted with permission.

Fig. 9.

Incubation of sucrose craving is associated with elevated dopamine-related neuronal signaling in several brain regions including the dorsolateral striatum. Rats responded in ten 2-hr daily sessions for a liquid drop of sucrose and a tone+light cue. Rats were tested for sucrose cue-reactivity by allowing them to respond in extinction conditions including the tone+light cue either 1 or 30 days into sucrose abstinence (DARPP32 study also included “no test” controls). Brains were examined after testing for Fos IR (left panel) or levels of total and threonine 34 phosphorylated DARPP32 (right panel). * Indicates significant difference from Day 1, p < .05. Left panel adapted from Grimm et al., 2016. Copyright 2015 by Springer-Verlag Berlin Heidelberg. Reprinted with permission. Right panel adapted from Grimm et al., 2018. Copyright 2018 by Springer Nature under the terms of the Creative Commons, creativecommons.org/licenses/by/4.0/.