Ralph DiLeone, PhD
Professor of Psychiatry and of Neuroscience
Research & Publications
Biography
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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, Worhunsky P, Costeines J, Driesen N, Rowland M, Nabulsi N, Trink R, Pittman B, Huang H, DiLeone R, Potenza M, Carson R, Angarita G, 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.
- Serotonin 5-HT2C receptors in the ventral subiculum regulate cocaine-evoked hyperactivity in ratsNeelakantan H, Stutz S, Bubar M, Sears R, DiLeone R, Cunningham K. Serotonin 5-HT2C receptors in the ventral subiculum regulate cocaine-evoked hyperactivity in rats Drug And Alcohol Dependence 2015, 156: e161-e162. DOI: 10.1016/j.drugalcdep.2015.07.440.
- Serotonin 5-HT2C receptors in the ventral subiculum regulate cocaine-evoked hyperactivity in ratsNeelakantan H, Stutz S, Bubar M, Sears R, DiLeone R, Cunningham K. Serotonin 5-HT2C receptors in the ventral subiculum regulate cocaine-evoked hyperactivity in rats Drug And Alcohol Dependence 2015, 156: e162. DOI: 10.1016/j.drugalcdep.2015.07.442.
- Maladaptive cortical serotonin (5-ht) 5-ht2a:5-ht2c receptor balance generates aberrant impulsivity and elevated cocaine cue reactivityAnastasio N, Stutz S, Fink L, Fox R, Sears R, Green T, DiLeone R, Moeller F, Cunningham K. Maladaptive cortical serotonin (5-ht) 5-ht2a:5-ht2c receptor balance generates aberrant impulsivity and elevated cocaine cue reactivity Drug And Alcohol Dependence 2014, 140: e4-e5. DOI: 10.1016/j.drugalcdep.2014.02.034.
- 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.
- S.11.2 - PREFRONTAL D1 NEURONS AND REGULATION OF FOOD INTAKELand B, Narayanan N, Liu R, Gianessi C, Brayton C, Grimaldi D, Sarhan M, Guarnieri D, Karl D, Aghajanian G, DiLeone R. S.11.2 - PREFRONTAL D1 NEURONS AND REGULATION OF FOOD INTAKE Behavioural Pharmacology 2013, 24: e13. DOI: 10.1097/01.fbp.0000434730.00153.f1.
- Transgenic Tools and Animal Models of Mental IllnessMonteggia L, Carlezon W, Dileone R. Transgenic Tools and Animal Models of Mental Illness 2013, 109-122. DOI: 10.1093/med/9780199934959.003.0008.
- An Introduction to the Special IssueSmall D, DiLeone R. An Introduction to the Special Issue Biological Psychiatry 2013, 73: 799-801. DOI: 10.1016/j.biopsych.2013.03.007.
- 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.
- Feeding as a Reward MechanismDiLeone R, Narayanan N, Guarnieri D. Feeding as a Reward Mechanism 2012, 47-60. DOI: 10.1007/978-1-4614-3492-4_4.
- Molecular adaptation in brain reward circuits in response to food restrictionGuarnieri D, Gray S, Maldonado-Aviles J, Brayton C, Trinko J, Dileone R. Molecular adaptation in brain reward circuits in response to food restriction Appetite 2011, 57: s18. DOI: 10.1016/j.appet.2011.05.179.
- NTS leptin signaling contributes to meal size control and suppression of food intake by intestinally-derived satiation signalsZhao S, Kanoski S, Guarnieri D, Dileone R, Hayes M, Grill H. NTS leptin signaling contributes to meal size control and suppression of food intake by intestinally-derived satiation signals Appetite 2011, 57: s48. DOI: 10.1016/j.appet.2011.05.300.
- IMPORTANT NEXT STEPS IN EVALUATING FOOD'S ADDICTIVE POTENTIALGEARHARDT A, DILEONE R, GRILO C, BROWNELL K, POTENZA M. IMPORTANT NEXT STEPS IN EVALUATING FOOD'S ADDICTIVE POTENTIAL Addiction 2011, 106: 1219-1220. DOI: 10.1111/j.1360-0443.2011.03454.x.
- Orexin/Hypocretin, Drug Addiction, and NarcolepsyDiLeone R, Sarhan M, Sharf R. Orexin/Hypocretin, Drug Addiction, and Narcolepsy 2011, 253-260. DOI: 10.1007/978-1-4419-8390-9_23.
- Functional Genomics and Models of Mental IllnessMonteggia L, Carlezon W, Dileone R. Functional Genomics and Models of Mental Illness 2011, 88-103. DOI: 10.1093/med/9780199798261.003.0007.
- Endogenous leptin signaling in the NTS is required for energy balance regulationHayes M, Skibicka K, Leichner T, Bence K, Dileone R, Grill H. Endogenous leptin signaling in the NTS is required for energy balance regulation Appetite 2009, 52: 836. DOI: 10.1016/j.appet.2009.04.092.
- P.2.28 Lack of leptin signalling in the ventral tegmental area accelerates starvation-induced hyperactivityVerhagen L, Luijendijk M, de Backer M, Koppers M, Garner K, DiLeone R, Adan R. P.2.28 Lack of leptin signalling in the ventral tegmental area accelerates starvation-induced hyperactivity European Neuropsychopharmacology 2009, 19: s56-s57. DOI: 10.1016/s0924-977x(09)70066-5.
- 2.501 Role of DeltaFosB in the development of L-DOPA-induced dyskinesia in a non-human primate model of Parkinson's diseaseBezard E, Berton O, Guigoni C, Dovero S, Kumar A, McClung C, DiLeone R, Nestler E. 2.501 Role of DeltaFosB in the development of L-DOPA-induced dyskinesia in a non-human primate model of Parkinson's disease Parkinsonism & Related Disorders 2007, 13: s142. DOI: 10.1016/s1353-8020(08)70775-2.
- Orexin/Hypocretin and Opioid DependenceDiLeone R. Orexin/Hypocretin and Opioid Dependence 2005, 327-337. DOI: 10.1007/0-387-25446-3_22.
- Inducible, Cell-Targeted Mutations In Mice: New Tools For Genetically Dissecting BehaviorNestler E, DiLeone R, Monteggia L. Inducible, Cell-Targeted Mutations In Mice: New Tools For Genetically Dissecting Behavior International Journal Of Comparative Psychology 2001, 14 DOI: 10.46867/c4vs3b.
- Efficient studies of long-distance Bmp5 gene regulation using bacterial artificial chromosomesDiLeone R, Marcus G, Johnson M, Kingsley D. Efficient studies of long-distance Bmp5 gene regulation using bacterial artificial chromosomes Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 1612-1617. PMID: 10677507, PMCID: PMC26483, DOI: 10.1073/pnas.97.4.1612.
- An extensive 3' regulatory region controls expression of Bmp5 in specific anatomical structures of the mouse embryo.DiLeone R, Russell L, Kingsley D. An extensive 3' regulatory region controls expression of Bmp5 in specific anatomical structures of the mouse embryo. Genetics 1998, 148: 401-8. PMID: 9475750, PMCID: PMC1459806, DOI: 10.1093/genetics/148.1.401.
- TheBmp8Gene Is Expressed in Developing Skeletal Tissue and Maps near theAchondroplasiaLocus on Mouse Chromosome 4DiLeone R, King J, Storm E, Copeland N, Jenkins N, Kingsley D. TheBmp8Gene Is Expressed in Developing Skeletal Tissue and Maps near theAchondroplasiaLocus on Mouse Chromosome 4 Genomics 1997, 40: 196-198. PMID: 9070944, DOI: 10.1006/geno.1996.4533.
- The Role of BMPs and GDFs in Development of Region‐Specific Skeletal StructuresaKing J, Storm E, Marker P, Dileone R, Kingsley D. The Role of BMPs and GDFs in Development of Region‐Specific Skeletal Structuresa Annals Of The New York Academy Of Sciences 1996, 785: 70-79. PMID: 8702185, DOI: 10.1111/j.1749-6632.1996.tb56245.x.