A General Method for Evaluating Incubation of Sucrose Craving in Rats

Abstract

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and relapse to food taking 1 . Food craving conceptualized in this way is akin to drug craving in response to drug-paired cues. A rich literature has been developed around understanding the behavioral and neurobiological determinants of drug craving; we and others have been focusing recently on translating techniques from basic addiction research to better understand addiction-like behaviors related to food [2][3][4] .As done in previous studies of drug craving, we examine sucrose craving behavior by utilizing a rat model of relapse. In this model, rats selfadminister either drug or food in sessions over several days. In a session, lever responding delivers the reward along with a tone+light stimulus. Craving behavior is then operationally defined as responding in a subsequent session where the reward is not available. Rats will reliably respond for the tone+light stimulus, likely due to its acquired conditioned reinforcing properties 5 . This behavior is sometimes referred to as sucrose seeking or cue reactivity. In the present discussion we will use the term "sucrose craving" to subsume both of these constructs.In the past decade, we have focused on how the length of time following reward self-administration influences reward craving. Interestingly, rats increase responding for the reward-paired cue over the course of several weeks of a period of forced-abstinence. This "incubation of craving" is observed in rats that have self-administered either food or drugs of abuse 4,6 . This time-dependent increase in craving we have identified in the animal model may have great potential relevance to human drug and food addiction behaviors. Here we present a protocol for assessing incubation of sucrose craving in rats. Variants of the procedure will be indicated where craving is assessed as responding for a discrete sucrosepaired cue following extinction of lever pressing within the sucrose self-administration context (Extinction without cues) or as responding for sucrose-paired cues in a general extinction context (Extinction with cues).

Chronic restraint stress causes a delayed increase in responding for palatable food cues during forced abstinence via a dopamine D1-like receptor-mediated mechanism

“…Finally, it is noteworthy that unstressed animals did not show a time-dependent increase in responding for food-associated cues, or “incubation of craving” [15]. We observed incubation only in stressed animals.…”

“…We observed incubation only in stressed animals. This was somewhat surprising given the large literature describing incubation of both drug and sucrose seeking [15, 47]; however, one potentially important methodological detail in our study is the use of a within-subjects design (i.e., incubation was assessed within the same animals tested twice). Studies reporting incubation of craving have primarily used between-subjects designs (i.e., separate groups of rats were tested in a single extinction test performed at different days during abstinence), which makes a direct comparison with the present study difficult.…”

“…We chose restraint because it is a well-established procedure that produces significant increases in plasma corticosterone levels [13, 14]. We chose an abstinence-based, as opposed to an extinction-based, model because we also wanted to determine whether chronic stress had any effect on “incubation of craving,” or the time-dependent increase in responding for food-associated cues [15], a phenomenon primarily assessed using an abstinence-based model.…”

Nicotine increases sucrose self‐administration and seeking in rats

“…While “incubation of craving” for sucrose and several abused drugs has been well-characterized, this is the first report we are aware of regarding an incubation of water craving. We have considered incubation to be reflective of enhanced motivational attribution to reinforcement-paired stimuli (Grimm et al 2011). Given these results with a water-paired cue in rats that were not water deprived at testing (nor during the vast majority of training), it appears that even the relatively low reinforcing efficacy of water (compared to sucrose) leads to incubation of craving and/or that a component of the incubated responding is not explicitly tied to reinforcement, but to some other aspect of learning.…”

Recent studies of the effects of sugars on brain systems involved in energy balance and reward: Relevance to low calorie sweeteners

“…During extinction, animals are motivated to respond either in the presence of or for the delivery of cues previously associated with the reward. Enhanced responding for cues at the later time point in abstinence has been noted following exposure to drugs of abuse, such as cocaine, as well as sucrose, a phenomenon termed “incubation of craving” [45]. Recent work shows age-related differences in incubation of sucrose craving, with adult and adolescent, but not young adolescent, rats demonstrating greater responding after the extended extinction period [46].…”