Browsing by Author "Starski, Phillip"

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    Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice
    (Frontiers Media, 2022-09-16) Starski, Phillip; Maulucci, Danielle; Mead, Hunter; Hopf, Frederic; Psychiatry, School of Medicine
    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 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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    Engagement for Alcohol Escalates in the 5-Choice Serial Reaction Time Task After Intermittent Access
    (bioRxiv, 2023-12-01) Starski, Phillip; Siegle, Addyson; Hopf, Frederic; Psychiatry, School of Medicine
    Uncontrollable binge drinking is becoming an increasingly prevalent issue in our society. This is a factor that plays a role in the development of alcohol use disorder (AUD). AUD impacts 15 million Americans annually, with approximately 88,000 dying from alcohol related deaths. There are several aspects of AUD that encourage a strong dependence on alcohol. Impulsivity, motivation, and attention are the primary behavioral facets we contribute to AUD. Many past studies have used the 5-Choice Serial Reaction Time Task (5-Choice) to analyze these types of behaviors using sugar as the reward. We have recently published a study where alcohol was used as a reward in the 5-Choice. 48 mice were trained to respond for alcohol in the 5-Choice, and the analyses for these animals were originally categorized by their alcohol preference and consumption. Upon looking at the data, we became more interested in a new way to classify these mice into groups. High engaged (HE) and low engaged (LE) mice were classified based on their number of correct responses in the last five late-stage sessions. During early-stage training, mice began to separate themselves into two groups based on their interaction with the task. The high-engaged (HE) mice were much more engaged with the task by having a high number of trials and correct responses, as well as a much lower percentage of omissions. The low engaged (LE) mice were not as engaged, this was apparent because of their lower number of trials and correct responses. They also had a much higher percentage of omissions in comparison to HE mice. LE mice presented no significant changes in late-stage training, while HE mice began responding and engaging more. These mice went through a period of intermittent access (IA), where they were allowed to drink alcohol in their cage for 3 weeks. After intermittent access, LE mice increased their responding which suggests an increase in motivation for alcohol as a reward. Engagement analysis presents two clearly different groups, one being motivated to work for alcohol and the other not wanting to work for this reward. These two distinct phenotypes in the 5-Choice could be used to model alcohol motivated behavior, which could help us further understand AUD.
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    Engagement for Alcohol Escalates in the 5-Choice Serial Reaction Time Task After Intermittent Access
    (Elsevier, 2024) Starski, Phillip; Siegle, Addyson; Hopf, Frederic; Psychiatry, School of Medicine
    Excessive intake plays a significant role in the development of alcohol use disorder and impacts 15 million Americans annually, with approximately 88,000 dying from alcohol related deaths. Several facets we contribute to alcohol use disorder include impulsivity, motivation, and attention. Previous studies have used the 5-Choice Serial Reaction Time Task (5-Choice) to analyze these types of behaviors using sugar, but recently we have published using 10% alcohol as the reward. This study analyzed 48 mice that were trained to respond for alcohol in the 5-Choice. All mice distributed and analyzed first by alcohol preference and then by consumption. Here, we became interested in a new classification called “engagement”. High-engaged and low-engaged mice were determined by the number of correct responses during final Late-Stage training sessions. Interestingly, during Early-Stage training, the mice began to separate themselves into two groups based on their interaction with the task. Throughout both training stages, high-engaged mice displayed a greater number of trials and correct responses, as well as a lower percentage of omissions compared to low-engaged mice. Following three weeks of intermittent access homecage drinking, low-engaged mice showed greater increase in perseverative responding relative to high-engaged. Additionally, low-engaged mice decreased their reward and correct latencies compared to high-engaged mice suggesting an increase in motivation for alcohol. Overall, engagement analysis presents two clearly different groups, with only one being motivated to work for alcohol. These two distinct phenotypes in the 5-Choice could be used to model alcohol motivated behavior, which could help us further understand alcohol use disorder.
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    Neural Activity in the Anterior Insula at Drinking Onset and Licking Relates to Compulsion-Like Alcohol Consumption
    (Society for Neuroscience, 2024-02-28) Starski, Phillip; Morningstar, Mitch D.; Katner, Simon N.; Frasier, Raizel M.; De Oliveira Sergio, Thatiane; Wean, Sarah; Lapish, Christopher C.; Hopf, F. Woodward; Psychiatry, School of Medicine
    Much remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role of the anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from the AIC promote compulsion-like intake in rats and are recruited in heavy-drinking humans during compulsion for alcohol, highlighting the importance of and need for more information about AIC activity patterns that support aversion-resistant responding. Single-unit activity was recorded in the AIC from 15 male rats during alcohol-only and compulsion-like consumption. We found three sustained firing phenotypes, sustained-increase, sustained-decrease, and drinking-onset cells, as well as several firing patterns synchronized with licking. While many AIC neurons had session-long activity changes, only neurons with firing increases at drinking onset had greater activity under compulsion-like conditions. Further, only cells with persistent firing increases maintained activity during pauses in licking, suggesting roles in maintaining drive for alcohol during breaks. AIC firing was not elevated during saccharin drinking, similar to lack of effect of AIC inhibition on sweet fluid intake in many studies. In addition, we observed subsecond changes in AIC neural activity tightly entrained to licking. One lick-synched firing pattern (determined for all licks in a session) predicted compulsion-like drinking, while a separate lick-associated pattern correlated with greater consumption across alcohol intake conditions. Collectively, these data provide a more integrated model for the role of AIC firing in compulsion-like drinking, with important relevance for how the AIC promotes sustained motivated responding more generally.