Ethanol Reinforcement Elicits Novel Response Inhibition Behavior in a Rat Model of Ethanol Dependence

Somkuwar, Sucharita S.; Quach, Leon W.; Quigley, Jacqueline; Purohit, Dvijen C.; Fannon, McKenzie J.; Koob, George F.; Mandyam, Chitra D.

doi:10.3390/brainsci8070119

Cited by 5 publications

(5 citation statements)

References 83 publications

(126 reference statements)

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“…This important advancement has allowed us to observe how motivated an animal was to wait during the intertrial interval, give a correct response, then retrieve the alcohol. Previous studies have trained animals to respond for alcohol in other behaviors such as differential reinforcement of low rates of responding (DRL) and progressive ratio tasks (Deehan et al, 2011;Somkuwar et al, 2018). While progressive ratio is valuable for measuring motivation, and DRL for impulsivity, the 5-CSRTT is designed to assess a broader range of measures in the same session.…”

Section: Discussionmentioning

confidence: 99%

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Starski

Maulucci

Mead

et al. 2022

Front. Behav. Neurosci.

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Alcohol use disorder (AUD) is related to excessive binge alcohol consumption, and there is considerable interest in associated factors that promote intake. AUD has many behavioral facets that enhance inflexibility toward alcohol consumption, including impulsivity, motivation, and attention. Thus, it is important to understand how these factors might promote responding for alcohol and can change after protracted alcohol intake. Previous studies have explored such behavioral factors using responding for sugar in the 5-Choice Serial Reaction Time Task (5-CSRTT), which allows careful separation of impulsivity, attention, and motivation. Importantly, our studies uniquely focus on using alcohol as the reward throughout training and testing sessions, which is critical for beginning to answer central questions relating to behavioral engagement for alcohol. Alcohol preference and consumption in male C57BL/6 mice were determined from the first 9 sessions of 2-h alcohol drinking which were interspersed among 5-CSRTT training. Interestingly, alcohol preference but not consumption level significantly predicted 5-CSRTT responding for alcohol. In contrast, responding for strawberry milk was not related to alcohol preference. Moreover, high-preference (HP) mice made more correct alcohol-directed responses than low-preference (LP) during the first half of each session and had more longer reward latencies in the second half, with no differences when performing for strawberry milk, suggesting that HP motivation for alcohol may reflect "front-loading." Mice were then exposed to an Intermittent Access to alcohol paradigm and retested in 5-CSRTT. While both HP and LP mice increased 5-CSRTT responding for alcohol, but not strawberry milk, LP performance rose to HP levels, with a greater change in correct and premature responding in LP versus HP. Overall, this study provides three significant findings: (1) alcohol was a suitable reward in the 5-CSRTT, allowing dissection of impulsivity, attention, and Frontiers in Behavioral Neuroscience 01 frontiersin.org Starski et al. 10.3389/fnbeh.2022.968359 motivation in relation to alcohol drinking, (2) alcohol preference was a more sensitive indicator of mouse 5-CSRTT performance than consumption, and (3) intermittent alcohol drinking promoted behavioral engagement with alcohol, especially for individuals with less initial engagement.

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Section: Discussionmentioning

confidence: 99%

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Starski

Maulucci

Mead

et al. 2022

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…This important advancement has allowed us to observe how motivated an animal was to wait during the intertrial interval, give a correct response, then retrieve the alcohol. Previous studies have trained animals to respond for alcohol in other behaviors such as differential reinforcement of low rates of responding (DRL) and progressive ratio tasks (43, 44). While progressive ratio is valuable for measuring motivation, and DRL for impulsivity, the 5-CSRTT is designed to assess a broader range of measures in the same session.…”

Section: Discussionmentioning

confidence: 99%

Low alcohol preferring mice have reduced task engagement during a waiting task for alcohol, which is enhanced by intermittent alcohol drinking

Starski

Maulucci

Mead

et al. 2022

Preprint

View full text Add to dashboard Cite

Alcohol use disorder (AUD) is related to excessive binge alcohol consumption, and there is considerable interest in associated factors that promote intake. AUD has many behavioral facets that enhance inflexibility toward alcohol consumption, including impulsivity, motivation, and attention. Thus, it is important to understand how these factors might promote responding for alcohol and can change after protracted alcohol intake. Previous studies have explored such behavioral factors using responding for sugar in the 5-Choice Serial Reaction Time Task (5-CSRTT), which allows careful separation of impulsivity, attention, and motivation. Importantly, our studies uniquely focus on using alcohol as the reward throughout training and testing sessions, which is critical for beginning to answer central questions relating to behavioral engagement for alcohol. Alcohol preference and consumption in C57BL/6 mice were determined from the first 9 sessions of 2-hour alcohol drinking which were interspersed among 5-CSRTT training. Interestingly, alcohol preference but not consumption level significantly predicted 5-CSRTT responding for alcohol. In contrast, responding for strawberry milk was not related to alcohol preference. Moreover, high-preference (HP) mice made more correct alcohol-directed responses than low-preference (LP) during the first half of each session and had more longer reward latencies in the second half, with no differences when performing for strawberry milk, suggesting that HP motivation for alcohol may reflect “front-loading.” Mice were then exposed to an Intermittent Access to alcohol paradigm and retested in 5-CSRTT. While both HP and LP mice increased 5-CSRTT responding for alcohol, but not strawberry milk, LP performance rose to HP levels, with a greater change in correct and premature responding in LP versus HP. Overall, this study provides three significant findings: 1) alcohol was a suitable reward in the 5-CSRTT, allowing dissection of impulsivity, attention, and motivation in relation to alcohol drinking, 2) alcohol preference was a more sensitive indicator of mouse 5-CSRTT performance than consumption, and 3) chronic alcohol drinking promoted behavioral engagement with alcohol, especially for individuals with less initial engagement.

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“…32 In addition, the same study showed that responding during protracted abstinence was reinforced using both sweetened ethanol solution and sucrose pellets. 32 Another recent study demonstrated that among Wistar rats displaying signs of ethanol addiction (e.g., high motivation and compulsive use despite devaluation of ethanol solution with quinine or ethanol responding using electric footshocks), only about 12%-15% chose ethanol over saccharin. 33 A third study showed that five cycles of ethanol vapor exposure (5 days/cycle, with 6 days between cycles) in food-restricted Long-Evans rats with no signs of compulsive ethanol use induced an increase in choice of 12% (w/v) ethanol over 0.1% saccharin during deprivation and discrete choice tests, but not during concurrent access.…”

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

“…A recent study that investigated impulsivity showed that ethanol vapor exposure induced an escalation in ethanol intake but not in sucrose pellet intake during 30‐min sessions in Wistar rats 32 . In addition, the same study showed that responding during protracted abstinence was reinforced using both sweetened ethanol solution and sucrose pellets 32 . Another recent study demonstrated that among Wistar rats displaying signs of ethanol addiction (e.g., high motivation and compulsive use despite devaluation of ethanol solution with quinine or ethanol responding using electric footshocks), only about 12%–15% chose ethanol over saccharin 33 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Sugar, a powerful substitute for ethanol in ethanol postdependent rats: Relevance for clinical consideration?

et al. 2021

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Sugar has been shown to be a powerful substitute for drugs in preclinical studies on addiction. However, the link between sugar intake and alcohol use disorder (AUD) is poorly understood. We assessed the influence of sucrose on ethanol drinking in both nondependent (ND) and dependent (D) Long–Evans rats during acute withdrawal using the postdependent state model. Ethanol (10%–40%) and sucrose (1%–4%) solutions were offered in an operant paradigm either independently or concurrently under ratio schedules of reinforcement. We showed that D rats displayed an enhanced motivation for both 10% ethanol solution (10E) and 4% sucrose solution (4S) as compared with ND rats, and a clear preference for 4S was observed in both groups. During acute withdrawal, D rats showed a strong motivation for 30% ethanol (30E), even when adulterated with quinine, but still preferred 4S despite the fact that a high level of negative reinforcement could be expected. However, when a premix solution (30E4S) was offered concurrently with 4S, the preference for 4S was lost in D animals, which consumed as much premix as 4S, whereas ND animals displayed preference for 4S. Altogether, those results suggest that reinforcing properties of sucrose surpass those of ethanol in D rats under acute withdrawal, which indicates that sugar is a powerful substitute for ethanol. Our results suggest that craving for sugar may be increased in AUD patients during withdrawal and raise the issue of dependence transfer from alcohol to sugar.

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Ethanol Reinforcement Elicits Novel Response Inhibition Behavior in a Rat Model of Ethanol Dependence

Cited by 5 publications

References 83 publications

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice

Low alcohol preferring mice have reduced task engagement during a waiting task for alcohol, which is enhanced by intermittent alcohol drinking

Sugar, a powerful substitute for ethanol in ethanol postdependent rats: Relevance for clinical consideration?

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