Rationale Conditioned cues can elicit relapse to drug- and food-seeking behavior over prolonged periods of abstinence. If seeking behavior depends on mesolimbic dopamine D1 receptors, blocking these receptors should reduce seeking behavior. Objectives We examined the effects of either systemic or intra-nucleus accumbens administration of the D1 antagonist SCH 23390 on extinction responding (sucrose seeking) by rats either 1 or 30 days into forced abstinence. Materials and methods Rats self-administered 10% sucrose paired with a tone+light cue for 10 days. After either 1 or 30 days of forced abstinence, rats received systemic (0, 1, 5, or 25 µg/kg IP) or bilateral nucleus accumbens core or shell (0.3 or 0.6 µg/site) injections of SCH 23390 prior to extinction testing. Results Saline-treated rats responded more during extinction following 30 vs. 1 day of forced abstinence (“incubation of craving”). Systemic SCH 23390 reduced sucrose seeking after 1 day of forced abstinence, significantly reducing responding following pretreatment with 1, 5, and 25 µg/kg SCH 23390, but only 25 µg/kg significantly reduced sucrose seeking after 30 days of forced abstinence. SCH 23390 (0.3 or 0.6 µg/site) in the core or shell of the nucleus accumbens reduced sucrose seeking in all groups. Conclusion Nucleus accumbens D1 receptors are involved in sucrose seeking, but it is not clear if they are involved in the incubation of craving. The fact that D1 antagonism reduced sucrose seeking across an extended period of abstinence may be of use for development of treatment strategies for relapse.

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).

Associations between nicotine in cigarettes and food consumption may alter the incentive value of food such that food cue-reactivity is exaggerated during abstinence from smoking. This effect may contribute to the weight gain associated with cessation of smoking. We examined the effects of nicotine (0.4 mg/kg base SC) paired (NPD) or unpaired (NUP) with 10 % sucrose self-administration (0.2 ml/delivery, 1h/day for 10 days) on self-administration response rate and intake as well as sucrose cue-reactivity following either 1 or 30 days of forced abstinence. Rats were administered the training dose of nicotine prior to a second, consecutive cue-reactivity session. NPD rats responded at over 3 times the rate for sucrose, and earned nearly twice the number of sucrose deliveries, as NUP rats or saline controls. Sucrose cue-reactivity was greater after 30 days, vs. 1 day of forced abstinence for all groups. History of nicotine exposure had no effect on sucrose cue-reactivity. However, the subsequent injection of nicotine increased sucrose cue-reactivity only in the NPD groups. There were no abstinent-dependent effects of nicotine challenge on sucrose cue-reactivity. A study conducted in parallel with water as the reinforcer revealed a less dramatic effect of nicotine on intake. There was no history or abstinence-dependent effects of nicotine on water cue-reactivity. Nicotine increases the reinforcing effects of sucrose and sucrose-paired cues when nicotine is present. An implication of these findings is that relapse to nicotine (cigarettes) could substantially elevate food cue-reactivity.

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 2-4 .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