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Ralph DiLeone, PhD

Professor of Psychiatry and of Neuroscience

Contact Information

Ralph DiLeone, PhD

Office Location

Mailing Address

  • Psychiatry

    Ribicoff Research Facilities, 34 Park St, CMHC

    New Haven, CT 06519

    United States

DiLeone Lab

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Research Summary

Our goal is to establish an understanding of the molecular and neuronal circuits that are responsible for controlling reward-related behavior. We seek to define brain mechanisms that regulate eating and activity relevant to weight regulation and the development of obesity. We also study neural mechanisms underlying drug addiction including translational projects aimed at treatment. Moreover, we have an in understanding the drive and motivation for physical activity that is a relatively understudied but key component of body weight regulation.

Specialized Terms: Addictions; Animal Behavior; Ethology; Animal Nutrition; Diseases and Disorders; Drug Abuse; Eating Disorders; Etiology; Evolution; Genetic Manipulation; Natural History; Obesity; Psychiatry

Extensive Research Description

Broadly, our research seeks to define the molecular and neural basis of behavior. Most of the work focused on neurocircuitry underlying responses to natural rewards (i.e. food) as well as drugs of abuse. We investigate the regulation and integration of these circuits with the longer term goal of understanding their relevance in disease, as well as the role that these circuits played in evolution. It is notable that the motivation to ingest food, though highly adaptive during most of our natural history, has proven to be incompatible with the current state of excess food supply. Similar circuits likely underlie our motivation for physical activity, including exercise. Understanding the motivational systems that control feeding and activity will give us insight into the molecular mechanisms of a complex behavior, and will ultimately serve to better define the etiology of obesity and eating disorders.

Our current translational studies on opiate use disorder are focused at evaluating specific therapeutics for their efficacy in animal models of dependence and drug seeking.


Our experiments and progress depend upon our ability to effectively monitor and manipulate neurons within the adult brain. We are active in using viral and transgenic techniques for conditional genetic analysis of neural function and behavior. The lab also leverages conditional viral approaches to evaluate activity of (via fiber photometry) or to manipulate (via optogenetics) specific circuits and neuronal types during behavior.

Coauthors

Research Interests

Feeding and Eating Disorders; Ethology; Neurobiology; Obesity; Psychiatry; Exercise; Substance Abuse Detection; Natural History; Glucose Metabolism Disorders; Animal Nutrition Sciences

Selected Publications

  • Distinct downstream targets of the medial prefrontal cortex underlie discrete antidepressant responses to ketamineShinohara R, Hare B, Liu R, Li J, Li X, Duman C, DiLeone R, Duman R. Distinct downstream targets of the medial prefrontal cortex underlie discrete antidepressant responses to ketamine Proceedings For Annual Meeting Of The Japanese Pharmacological Society 2022, 95: 1-o-011. DOI: 10.1254/jpssuppl.95.0_1-o-011.
  • GluN2B‐containing NMDA Receptors on Sst‐interneurons act as Initial Cellular Trigger for Antidepressant Actions of KetaminePothula S, Liu R, Wu M, Sliby A, DiLeone R, Duman R. GluN2B‐containing NMDA Receptors on Sst‐interneurons act as Initial Cellular Trigger for Antidepressant Actions of Ketamine The FASEB Journal 2021, 35 DOI: 10.1096/fasebj.2021.35.s1.02392.
  • The Roles of Endogenous Opioid System in the Antidepressant Actions of KetamineJiang C, DiLeone R, Pittenger C, Duman R. The Roles of Endogenous Opioid System in the Antidepressant Actions of Ketamine Biological Psychiatry 2021, 89: s385. DOI: 10.1016/j.biopsych.2021.02.956.
  • Vitamin D Modulation of Midbrain Dopamine Function: A 11C-PHNO PET Study in Healthy HumansFlores J, Flores J, Flores J, Worhunsky P, Costeines J, Driesen N, Rowland M, Nabulsi N, Trink R, Trink R, Trink R, Pittman B, Huang H, Huang H, Huang H, DiLeone R, Potenza M, Carson R, Angarita G, Angarita G, Angarita G, Malison R, Malison R, Malison R. Vitamin D Modulation of Midbrain Dopamine Function: A 11C-PHNO PET Study in Healthy Humans Biological Psychiatry 2021, 89: s253. DOI: 10.1016/j.biopsych.2021.02.634.
  • Ketamine Increases vmPFC Activity: Effects of (R)- and (S)-Stereoisomers and (2R,6R) Hydroxynorketamine MetaboliteHare B, Pothula S, DiLeone R, Duman R. Ketamine Increases vmPFC Activity: Effects of (R)- and (S)-Stereoisomers and (2R,6R) Hydroxynorketamine Metabolite Biological Psychiatry 2020, 87: s191. DOI: 10.1016/j.biopsych.2020.02.499.
  • Medial Nucleus Accumbens Projections to the Ventral Tegmental Area Control Food ConsumptionBond CW, Trinko R, Foscue E, Furman K, Groman SM, Taylor JR, DiLeone RJ. Medial Nucleus Accumbens Projections to the Ventral Tegmental Area Control Food Consumption Journal Of Neuroscience 2020, 40: 4727-4738. PMID: 32354856, PMCID: PMC7294796, DOI: 10.1523/jneurosci.3054-18.2020.
  • Ronald S. Duman, PhD (1954–2020)Taylor J, DiLeone R, Picciotto M. Ronald S. Duman, PhD (1954–2020) Nature Neuroscience 2020, 23: 595-595. PMCID: PMC7190563, DOI: 10.1038/s41593-020-0629-3.
  • Striatal dopamine regulates systemic glucose metabolism in humans and miceTer Horst KW, Lammers NM, Trinko R, Opland DM, Figee M, Ackermans MT, Booij J, van den Munckhof P, Schuurman PR, Fliers E, Denys D, DiLeone RJ, la Fleur SE, Serlie MJ. Striatal dopamine regulates systemic glucose metabolism in humans and mice Science Translational Medicine 2018, 10 PMID: 29794060, DOI: 10.1126/scitranslmed.aar3752.
  • F98. Stimulation of Drd1 Expressing Principle Neurons in the Prefrontal Cortex Produces Rapid and Long-Lasting Antidepressant Effects and is Necessary for the Response to KetamineHare B, Liu R, Shinohara R, DiLeone R, Duman R. F98. Stimulation of Drd1 Expressing Principle Neurons in the Prefrontal Cortex Produces Rapid and Long-Lasting Antidepressant Effects and is Necessary for the Response to Ketamine Biological Psychiatry 2018, 83: s275-s276. DOI: 10.1016/j.biopsych.2018.02.711.
  • Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food IntakeZhu X, Ottenheimer D, DiLeone RJ. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake Frontiers In Behavioral Neuroscience 2016, 10: 66. PMID: 27147989, PMCID: PMC4828436, DOI: 10.3389/fnbeh.2016.00066.
  • Medial prefrontal D1 dopamine neurons control food intakeLand BB, Narayanan NS, Liu RJ, Gianessi CA, Brayton CE, M Grimaldi D, Sarhan M, Guarnieri DJ, Deisseroth K, Aghajanian GK, DiLeone RJ. Medial prefrontal D1 dopamine neurons control food intake Nature Neuroscience 2014, 17: 248-253. PMID: 24441680, PMCID: PMC3968853, DOI: 10.1038/nn.3625.
  • Prefrontal D1 dopamine signaling is required for temporal controlNarayanan NS, Land BB, Solder JE, Deisseroth K, DiLeone RJ. Prefrontal D1 dopamine signaling is required for temporal control Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 20726-20731. PMID: 23185016, PMCID: PMC3528521, DOI: 10.1073/pnas.1211258109.
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