Research Focus

My research interests are concerned with the neurobiological basis of motivation and addiction research.

Relapse-Suppressing Brain Mechanisms:

Drug addiction and alcoholism are a chronic relapsing disorder of compulsive drug and alcohol use. Significant effort has been dedicated to reveal neurobehavioral factors that promote relapse. Despite such effort, existing anti-relapse medications are only moderately effective. An alternative research strategy may thus prove beneficial.

I therefore decided to pursue a strategy shift by focusing on neurobehavioral factors that suppress – rather than promote – relapse. Specifically, I hypothesized that in contrast to the well-established relapse-promoting actions of cues linked to drug availability, cues linked to drug non-availability or “omission” suppress relapse. To test this hypothesis, I developed an “omission cue-induced suppression (OCIS) paradigm”, and conducted a series of experiments to characterize the relapse-suppressing actions of omission cues. This work has demonstrated that omission cues indeed suppress relapse in laboratory animals (rats). Importantly, relapse-suppression by omission cues holds (1) across two distinct classes of abused drugs (cocaine and alcohol), (2) for all major modes of relapse-promotion (drugs, stress and drug cues), as well as (3) under conditions linked to particularly high relapse risk (e.g., alcohol withdrawal in dependent animals).

The OCIS paradigm provides a unique platform to identify as yet poorly characterized brain mechanisms that inhibit learned (conditioned) response – such as drug and alcohol relapse – and thus to provide new insights for improving anti-relapse strategies. For this premise, my laboratry have recently found that OCIS is mediated by omission "cue-activated" neurons within the medial prefrontal cortex (mPFC) – a region implicated in cognitive control of drug craving in addicts. To further explore the relapse-suppressing brain mechanisms, we are currently undertaking seveal NIH-funded projects that collectively seek to establish medial prefrontal cortical (1) neural phenotypes, (2) neurochemical signals and (3) neural circuits mediating relapse-suppression by drug omission cues.

Neurobiology of Compulsive Appetite:

Obesity and pathological overeating have received increasing recognition as disorders of “food addiction” because of their similarities to substance dependence in behavioral manifestations and neurobiological underpinnings. However, the applicability of this nosology remains a matter of debate. Our research findings to date suggest that the nosology of addiction is most applicable to phenotypes of eating disorders that are characterized by "compulsive appetite" such as binge-eating disorder and bulimia nervosa. We are currently conducting experiments to determine the epigenetic factors contributing to addiction-like food motivation.

Method development:

In addition, my laboratory has engaged in several lines of method development efforts including:

1. Cell type-specific and activity-dependent molecular profiling of a medical treatment. The objective is to develop a tool for investigating ‘functional’ epigenetic changes in neurons (rather than homogenized brain samples as commonly being practiced) associated with therapeutic actions of a medication.  This will be achieved by combining recent advances in transgenic technology, neural purification via fluorescent activated cell sorting (FACS), next-generation sequencing (NGS), and bioinformatics.

2. A unified system of wireless optogenetics and brian microdialysis for afferent-specific neurochemical profiling in freely moving animals. While optogenetics allows manipulation of biological systems at a high degree of cell type and circuit level specificity, its neurochemical impacts largely remain uncharacterized and is inferred – indirectly – on the effects of pharmacological manipulation (antagonists) due to the lack of an adequate tool. Given that the predominant mode of cellular interactions is neurochemical, the development of such tools will facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. We aim to fulfill these goals through the development of a unified system for wireless optogenetics and brain microdialysis.

Education

B.A., Psychology (Biological), University of California at Berkeley
Ph.D., Psychology (Biological), University of Chicago

Professional Experience

2015 –             Assistant Professor of MCN, TSRI

2013 – 2015    Staff Scientist, TSRI (Dr. Friedbert Weiss, PI)   

2012 – 2013    Senior Research Associate (Dr. Friedbert Weiss, PI)

2009 – 2012    Staff Scientist, University of Maryland Baltimore (Dr. Greg I. Elmer, PI)

2003 – 2008    Post-Doctoral Fellow, NIDA/NIH/IRP (Dr. Roy A. Wise, advisor)

 

Awards & Professional Activities

RESEARCH SUPPORT:

R01AA023183 (NIAAA/NIH), Nobuyoshi Suto (PI), 03/10/15 - 02/29/20 Relapse-suppressing brain mechanisms in alcoholism: role of the mPFC: The purpose of this grant is to combine a novel behavioral paradigm and advanced molecular, neurochemical, neuropharmacological, as well as neuroanatomical techniques to determine brain mechanisms that actively suppress (as opposed to promote) alcohol relapse in dependent subjects (rats) undergoing withdrawal – conditions linked to a high relapse risk. Since the majority of drug addiction research has focused on factors that promote relapse, the expected results could provide novel insights into alcohol craving and relapse, and aid to improve relapse-suppression strategy.

R01DA037294 (NIDA/NIH), Nobuyoshi Suto (PI), 04/01/15 - 12/31/19 Cocaine omission cues suppress relapse: role of the medial prefrontal cortex. Cocaine addiction is a chronic relapsing disorder characterized by compulsive cocaine use. The purpose of this grant is to combine a novel behavioral paradigm and advanced molecular, neurochemical, pharmacological, neuroanatomical as well as pharmacogenetic techniques to determine brain mechanisms that actively suppress “addiction-like” cocaine seeking in rats. Since the majority of drug addiction research has focused on factors that promote relapse, our expected results could provide novel insights into the neurobiological underpinnings of cocaine craving and relapse, and aid to improve anti-relapse medication.   

R21DA033533 (NIDA/NIH), Nobuyoshi Suto (PI), 01/15/13 - 9/30/15Relapse-suppressing neuronal ensembles in cocaine addiction. This exploratory and developmental project is designed to establish an empirical foundation on which to build future, more systematic investigations of brain mechanisms mediating omission cue-induced suppression (OCIS) of cocaine seeking. The objectives are: 1) to establish a ‘brain map’ of omission cue-induced neural activation in the brain reward circuitry, and 2) to study links between omission cue-induced neural activation in the medial prefrontal cortex and the OCIS.

Selected References

Suto N. Elmer GI. Wang B. You Z-B. Wise RA. (2013) Bidirectional modulation of cocaine-expectancy by phasic glutamate changes in the nucleus accumbens. Journal of Neuroscience. 33: 9050-55. PMCID: PMC3698054.

Ecke LE. Elmer GI. Suto N. (2012). Cocaine self-administration is not dependent on mesocortical alpha1 noradrenergic signal.  NeuroReport. 23: 325-30. PMCID: PMC3296896.

Suto N. Wise RA. (2011). Satiating effects of cocaine are controlled by dopamine actions in the nucleus accumbens core.  Journal of Neuroscience.  31: 17917-22.  PMCID: PMC3264394.

Suto N. Wise RA. Vezina P. (2011). Dorsal as well as ventral striatal lesions affect levels of intravenous cocaine and morphine self-administration in rats. Neuroscience Letters. 493: 29-32. PMCID: PMC3065204.

Suto N. You Z-B. Ecke LE. Wise RA.  (2010) Extracellular levels of dopamine and glutamate in the nucleus accumbens core and shell associated with lever-pressing during cocaine self-administration, ‘yoked’ administration of cocaine, and extinction.  Psychopharmacology. 211: 267-75. PMCID: PMC3177323.

Suto N. Ecke LE. Wise RA. (2009): Control of within-binge cocaine-seeking by dopamine-glutamate interaction in the core of nucleus accumbens.  Psychopharmacology. 205: 431-439. PMCID: PMC3150710.

Suto N. Tanabe LM. Austin JD. Creekmore E. Pham CT. Vezina P.  (2004): Previous exposure to psychostimulants enhances the reinstatement of cocaine seeking by nucleus accumbens AMPA.  Neuropsychopharmacology.  29: 2149-2159. PMID: 15266353.

Suto N. Tanabe LM. Austin JD. Creekmore E. Vezina P. (2003): Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in an NMDA, AMPA/kainate and metabotropic glutamate receptor dependent manner. Neuropsychopharmacology.  28: 629-39. PMID: 12655307.

Suto N. Austin JD. Tanabe LM. Kramer MK. Wright DA. Vezina P.  (2002): Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in a D1 dopamine receptor dependent manner.  Neuropsychopharmacology.  27: 970-9. PMID: 12464454.

Vezina P. Lorrain DS. Arnold GM. Austin JD. Suto N. (2002): Sensitization of midbrain dopamine neuron reactivity promotes the pursuit of amphetamine.  Journal of Neuroscience. 22: 4654-62. PMID: 12040071.

Suto N. Austin JD. Vezina P.  (2001): Locomotor response to novelty predicts a rat’s propensity to self-administer nicotine.  Psychopharmacology.  158: 175-80. PMID: 11702091.