Individual differences in substance use

Explore our research on individual differences in substance use, focusing on how personal behavioral and biological factors influence addiction and treatment responses. Learn about our efforts to improve and personalize substance use disorder treatments.

Why Is This Field Understudied?

Despite the high morbidity, mortality, and economic burdens attributed to substance use globally, current treatment strategies have shown only marginal effectiveness. The complexity of tobacco, alcohol, and illicit substance use, coupled with cultural, social, behavioral, and biological factors, calls for novel basic science approaches. One such approach is the focus on individualized prevention and treatment strategies. There is a significant gap in translating preclinical research into effective cessation and relapse prevention treatments, partly due to a lack of understanding of individual differences along the substance use continuum. Our laboratory is dedicated to identifying these individual variations to improve treatment efficacy and patient outcomes.

Why We Study Individual Differences in Substance Use

Our research is committed to understanding why some individuals are more susceptible to substance use and addiction than others. We believe that by focusing on the unique behavioral and biological markers of each person, we can develop more personalized and effective treatments. For instance, our recent studies have demonstrated that individual responses to stress can significantly predict their tendency towards heroin use or their reaction to nicotine cessation treatments. By studying these individual differences, we aim to contribute to a more nuanced understanding of substance use disorders, leading to interventions that are tailored to each person’s unique makeup.

Recent Progress and Methodologies

Our laboratory has developed a preclinical approach emphasizing individual variability in behavioral and biological mechanisms associated with substance use disorders. This approach, based on the established preclinical drug self-administration model and behavioral economics, allows us to assess individual economic demand for substances and understand the underlying predictive, prognostic, and protective factors. We employ a multivariate systems perspective particularly suited to studying individuals. Our studies often require long-term commitments due to various phases, including baseline assessments, pre-training, surgeries, establishment of drug self-administration, and phases modeling abstinence and relapse.

Contributions and Future Directions

We have recently demonstrated our ability to identify key biomarkers involved in stress-induced heroin self-administration and predict individual responses to nicotine cessation treatments. Moving forward, we aim to continue this line of research by expanding our understanding of phenotypic profiles of individuals vulnerable to stress and substance use comorbidity. This includes employing computational approaches and extensive collaborations to assess biological markers of stress in individuals prone to substance use. Our research, firmly grounded in scientific rigor and commitment to uncovering individual differences, aims to offer significant contributions to the field of addiction research and treatment.

Hypothesized stress and heroin use model

(A) We hypothesize that vulnerability to stress is a contributing factor in propensity to use and abuse heroin. Although many individuals experience traumatic stress, not many progress to use and abuse heroin. We hypothe-sized that those individuals that are exposed to traumatic stress and are vulnerable to traumatic stress (exhibiting long lasting symptoms similar to PTSD – hyperarousal, hypervigilance, social withdrawal, and cognitive alterations) have higher risk of using and abusing heroin after exposure to traumatic stress. (B) We further hypothesize that we can successfully mod-el these individual effects in a newly developed preclinical animal model of traumatic stress and heroin use comorbidity. That is, rats that are more vul-nerable to stress will self-administer more heroin after the stress exposure.

Unraveling the Ties Between Stress and Heroin Demand: A Focused Inquiry

In the pursuit of understanding the complex dynamics of addiction, our recent study, “Individual Vulnerability to Stress Is Associated With Increased Demand for Intravenous Heroin Self-administration in Rats,” represents a significant stride. This research delves into the intricate relationship between individual stress vulnerability and the propensity for heroin use, addressing a crucial gap in addiction science.

The study’s innovative approach hinges on a within-subjects design, employing a rodent model to simulate the stress and addiction interplay observed in humans. By exposing male rats to a controlled stressor — intermittent swim stress — we meticulously documented each subject’s biological and behavioral responses. The focus was on individual variation, acknowledging that each organism’s unique stress profile might hold the key to understanding its subsequent drug-seeking behavior.

Biological markers, such as corticosterone levels, and behavioral metrics from open field social exploration and forced swim tests, provided a multidimensional view of stress reactivity. This methodological rigor allowed for a nuanced analysis, revealing how these diverse stress responses could predict the magnitude of heroin demand in these animal models.

The significance of this study is multifaceted. Firstly, it methodically demonstrates that individual stress-related biological and behavioral markers can indeed forecast heroin demand, highlighting the potential for targeted intervention strategies. Secondly, by emphasizing individual variability, the research underscores the necessity for a personalized approach in treating substance use disorders, moving beyond generalized treatments to those that consider each subject’s unique stress and behavioral profile.

As we disseminate these findings, our objective is clear: to contribute a piece to the larger puzzle of addiction research. By understanding the underpinnings of stress-induced drug demand, we aim to enhance predictive models of addiction vulnerability and refine therapeutic strategies, ultimately advancing the field towards more individualized and effective treatments.

References

2023

Assessment of ethanol and nicotine interactions using a reinforcer demand modeling with grouped and individual levels of analyses in a long-access self-administration model using male rats

Christopher L. Robison, Nicole Cova, Victoria Madore, and 3 more authors

Frontiers in Behavioral Neuroscience, Jul 2023

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Previous reports have indicated the reciprocal effects of nicotine and ethanol on their rewarding and reinforcing properties, but studies using methodological approaches resembling substance use in vulnerable populations are lacking. In our study, rats first self-administered ethanol, and their sensitivity to ethanol’s reinforcing effects was assessed using a reinforcer demand modeling approach. Subsequently, rats were equipped with intravenous catheters to self-administer nicotine, and their sensitivity to nicotine’s reinforcing effects was evaluated using the same approach. In the final phase, rats were allowed to self-administer ethanol and nicotine concurrently, investigating the influence of one substance on the rate of responding for the other substance. Group analyses revealed notable differences in demand among sucrose, sweetened ethanol, and ethanol-alone, with sucrose demonstrating the highest demand and ethanol-alone exhibiting greater sensitivity to changes in cost. At the individual level, our study finds significant correlations between rats’ demand for sucrose and sweetened ethanol, suggesting parallel efforts for both substances. Our individual data also suggest interconnections in the elasticity of demand for sweetened ethanol and ethanol-alone, as well as a potential relationship in price response patterns between ethanol and nicotine. Furthermore, concurrent self-administration of ethanol and nicotine at the group level displayed reciprocal effects, with reduced responding for nicotine in the presence of ethanol and increased responding for ethanol in the presence of nicotine. This study provides valuable insights into modeling the co-use of ethanol and nicotine and assessing their interaction effects using reinforcer demand modeling and concurrent self-administration or noncontingent administration tests. These findings contribute to our understanding of the complex interplay between ethanol and nicotine and have implications for elucidating the underlying mechanisms involved in polydrug use.

2020

Assessment of individual differences in response to acute bupropion or varenicline treatment using a long-access nicotine self-administration model and behavioral economics in female rats

Theodore Kazan, Christopher L. Robison, Nicole Cova, and 2 more authors

Behavioural Brain Research, Jul 2020

Publisher: Elsevier

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Bupropion and varenicline are widely prescribed pharmacological treatments for smoking cessation. These treatments are only marginally effective in clinical populations but most preclinical studies show that they are effective in decreasing self-administration in rats on a group level. The present study investigated individual differences in responding to bupropion or varenicline in a preclinical model of long-access to nicotine (0.03 mg/kg/inf; 12 h/day) in female rats. Rats were first assessed for their individual economic demand for nicotine and for their individual performance in open field and elevated plus maze prior to nicotine access and during withdrawal. Rats were then tested for the acute effects of bupropion, varenicline, and yohimbine. We found that neither bupropion nor varenicline decreased responding for nicotine on test days. On the contrary, a moderate dose of bupropion (30 mg/kg) significantly increased responding for nicotine. We also found that rats with higher demand for nicotine were more sensitive to pretreatment with yohimbine which resulted in increased responding for nicotine during the dose-effect tests. Finally, we show that rats that had a higher demand for nicotine also were more persistent in seeking nicotine during extinction and reinstatement tests with nicotine or yohimbine as triggers. Our findings suggest that the length of access to daily nicotine may be an important factor underlying the response to pharmacological treatments like bupropion or varenicline. Future studies modeling chronic treatment approaches that include both sexes will be needed to further extend our findings.

2019

Individual Vulnerability to Stress Is Associated With Increased Demand for Intravenous Heroin Self-administration in Rats.

Nathaniel P. Stafford, Theodore N. Kazan, Colleen M. Donovan, and 3 more authors

Frontiers in Behavioral Neuroscience, Jun 2019

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Opioid use is a widespread epidemic, and traumatic stress exposure is a critical risk factor in opioid use and relapse. There is a significant gap in our understanding of how stress contributes to heroin use, and there are limited studies investigating individual differences underlying stress reactivity and subsequent stress-induced heroin self-administration. We hypothesized that greater individual vulnerability to stress would predict higher demand for heroin self-administration in a within-subjects rodent model of stress and heroin use comorbidity. Male rats were exposed to inescapable intermittent swim stress ({I}SS}) and individual biological (corticosterone) or behavioral [open field, social exploration, and forced swim tests ({FSTs})] measures were assessed before and after the stress episode. Individual demand for self-administered heroin (0.05 mg/kg/infusion; 12-h sessions) was assessed using a behavioral economics approach followed by extinction and reinstatement tests triggered by stress re-exposure, non-contingent cue presentations, and yohimbine (0, 1.0, or 2.5 mg/kg). We found that behavioral, biological, and a combination of behavioral and biological markers sampled prior to and after the stress episode that occurred weeks before the access to heroin self-administration predicted the magnitude of individual demand for heroin. Non-contingent presentation of cues, that were previously associated with heroin, reinstated heroin seeking in extinction. For the first time, we show that individual biological response to an ecologically relevant stressor in combination with associated behavioral markers can be used to predict subsequent economic demand for heroin.