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Contains fulltext : 175064.pdf (Publisher’s version ) (Closed access) Alcohol use disorder (AUD) is characterized by excessive alcohol use and persistent alcohol seeking despite knowledge of its negative consequences. Importantly, AUD typically develops after chronic excessive alcohol use in a subgroup of individuals who drink alcohol, suggesting that AUD results from an interaction between individual vulnerability and prolonged alcohol exposure. The present study assessed the contribution of prolonged exposure to alcohol and individual levels of alcohol intake to the development of loss of control over alcohol seeking in a conditioned suppression model. To investigate the impact of prolonged alcohol exposure, conditioned suppression of alcohol seeking was assessed after 2 and 4 months of intermittent alcohol access (IAA) in a subgroup of rats drinking moderate amounts of alcohol. We observed that suppression of alcohol seeking was reduced after 4 months compared with 2 months of IAA. The influence of individual levels of alcohol intake on loss of control over alcohol seeking was subsequently determined by assessing conditioned suppression in subgroups of low and high alcohol drinking rats. Unlike the low alcohol drinking rats, the high alcohol drinking rats showed aversion-resistant alcohol seeking after 2 months of IAA, although both groups showed comparable levels of conditioned freezing. These findings show that the development of loss of control over alcohol seeking, a key characteristic of AUD in humans, is dependent on both the extent of alcohol exposure and the individual's propensity to consume alcohol.

In the resurgence preparation, extinguished alcohol-maintained responding increases when food reinforcement introduced into the same context during extinction is also subsequently removed. However, drug and nondrug reinforcers may often be obtained in separate specific contexts. Accordingly, we aimed to determine whether extinguished behavior previously maintained by alcohol would increase upon elimination of nondrug reinforcement within a multiple schedule arranging distinct discriminative stimulus contexts of food and alcohol availability. In Experiment 1, rats earned food or alcohol in alternating stimulus contexts within a multiple schedule. First, alcohol-maintained responding was extinguished and then food deliveries in the alternating component were also discontinued. Extinguished alcohol-maintained responding increased upon discontinuation of food deliveries. However, periods of alcohol availability alternated with periods of extinction during a portion of training; thus, elimination of food reinforcers during the resurgence test may have inadvertently served as a cue for alcohol availability. In Experiment 2, the training phase that complicated interpretation of the results of Experiment 1 was eliminated. Alcohol-maintained responding again increased when food-maintained responding was placed on extinction in the other component. The present results indicate that loss of nondrug reinforcement in one discriminative context can increase extinguished alcohol seeking in another context and that multiple schedules of reinforcement might be useful for examining such effects.