SUMMARY
Nobu Suto, Ph.D., studies the neurobiological basis of compulsive behavior and relapse in drug addiction and food addiction. The goal of his research is to discover "druggable" targets for improving antiaddiction medications. Such medications may counter compulsive behavior and relapse across drug and food addiction through cell type-specific and neurocircuit-specific profiling and through functional interrogation of behaviorally relevant brain substrates and mechanisms. For the purposes of Dr. Nobu's research, drug addiction includes stimulant, alcohol, opioid and nicotine use disorders, while food addiction is understood as a subset of obesity that includes eating disorders such as binge-eating disorder, bulimia nervosa and anorexia nervosa with binge-eating subtype.
In his first laboratory at The Scripps Research Institute in La Jolla, California, Dr. Suto drew on his academic training in biological psychology and behavioral neuroscience to develop murine models of addictive behavior using classical and operant conditioning in wild-type and transgenic animals. At Mayo Clinic, Dr. Suto uses molecular, chemogenetic and optogenetic techniques, neurochemical techniques, and neurocircuitry and anatomical techniques to build on his previous research. His team also conducts gene sequencing and editing, bioinformatics and data science, and analytical chemistry. This cross-disciplinary integration is achieved through ongoing collaborations with researchers in academia and industry in the United States and around the world.
As a program director and principal investigator, Dr. Suto has received seven National Institutes of Health (NIH) grants to date and is seeking further research funding to improve addiction medicine and treatment.
Focus areas
- Brain mechanisms driving compulsive behavior across drug and food addiction. One of the major obstacles to successfully treating drug addiction and food addiction is compulsive intake of drugs or food that persists despite negative consequences or "punishments." Dr. Suto's laboratory has found that akin to compulsive drug or food intake in people who have these behavioral issues, rats develop punishment-resistant "compulsive" food intake after extensive exposures to either drugs of abuse — for example, cocaine, alcohol, morphine or nicotine — or "obesogenic" diets high in fat, sugar or both.
Based on this animal model linking compulsive behavior across drug addiction and food addiction, Dr. Suto has developed several NIH-funded research projects to determine neurocircuit reorganization and neurochemical and transcriptional maladaptation in the brain that manifest as compulsive behavior in addictive disorders. He expects that these research projects will determine common brain substrates that drive compulsive food intake in rats with a history of extensive drug exposure, obesogenic diet exposure or both. These substrates could then be used as druggable targets to counter compulsive behavior in both drug addiction and food addiction.
- Brain mechanisms driving the intensification of drug craving during prolonged abstinence. Patients recovering from substance use disorders often report that their drug or alcohol cravings intensify while successfully undergoing even prolonged abstinence. These intensifying cravings make it difficult to prevent relapse. However, the brain substrates driving the intensification of such cravings remain unknown. Dr. Suto's laboratory has found that drug-reactive neurons in the brain's reward circuits undergo unique transcriptional changes. These changes are distinct from corresponding changes in adjacent nonreactive neurons. Changes in the reactive neurons drive intensification of alcohol and opioid craving in abstinent rats. These functional units of neurons — called neuronal ensembles or memory engram cells — thus can serve as cellular targets to identify functional gene targets for antirelapse medications.
Based on these results, Dr. Suto has developed NIH-funded projects to determine transcriptional maladaptation that is functionally linked to increasingly intense alcohol and opioid cravings. His laboratory also is developing research projects to determine the neurocircuitry and neurochemical maladaptation that drives the intensification of drug cravings during prolonged abstinence. Dr. Suto expects that these research projects will determine brain substrates that are functionally linked to the intensification of drug cravings in people with substance use disorders who have successfully abstained from substance use for weeks, months or even years. These substrates could then be used as druggable targets to develop anticraving medications to treat people with different substance use disorders.
- Antidrug relapse brain mechanisms. Drug addiction is a chronic relapsing disorder of compulsive drug use, and drug relapse prevention is a major goal of drug rehabilitation programs. Significant effort has been dedicated to revealing environmental and brain factors that can trigger drug relapse. But existing antidrug relapse medications are still only moderately effective. Dr. Suto's laboratory is therefore pursuing a different strategy. Instead of focusing on environmental and brain factors that might trigger drug relapse, the research team is looking for factors that might suppress it.
To accomplish this novel goal, Dr. Suto's laboratory first established a murine model for relapse suppression. The model uses environmental cues that signal drug unavailability, also called drug omission cues. Dr. Suto has developed several NIH-funded research projects based on this model. His laboratory also has identified that drug omission cues recruit neurons in the infralimbic cortex — a brain structure implicated in executive functions — to suppress relapse. Using these omission cue-reactive neurons as the cellular target for relapse-suppression, Dr. Suto's laboratory has been conducting further experiments to identify relapse-suppressing neurocircuitries and neurochemicals. Dr. Suto expects that these studies will determine brain substrates that actively suppress, rather than promote, drug relapse, thereby possibly serving as druggable targets for antidrug relapse medication that could facilitate — if not mimic — the brain's natural ability to suppress drug craving, seeking and intake.
Significance to patient care
Drug addiction and food addiction share many of the same behavioral issues. For example, they both involve compulsive use of drugs or food. And many people relapse after treatment. It is likely that they are driven by similar processes or substances in the brain. Understanding what these addictions have in common within the brain may lead to new medicines that better target the addiction. This may make treatment even more effective against substance use disorders, eating disorders and obesity.