Our research program is directed at understanding changes in dopamine neurons and their connections by genetic abnormalities and by exposure to drugs or stressors at different times in life.

1) Dopamine Development and Resilience: Mesocorticolimbic dopamine circuitry has extensive influence over the onset of psychopathologies such as schizophrenia, depression, and addiction. We study variations in the netrin-1 guidance cue system at specific developmental stages to determine how they alter the establishment of dopamine circuitry. We are interested in how these developmental events affect dopamine function and behavior in adulthood, and their role mediating resilience to psychopathology in both animal models and in translational human studies.

2) Drugs and Adolescent Brain Development:  One of our goals is to understand how initiation of drug use in adolescence, in comparison to adulthood, increases vulnerability to developing addiction.
We identified the first known mediator of adolescent prefrontal cortex development, the netrin-1 receptor, DCC, and are currently studying how DCC-dependent mechanisms act as a target for gene-environment interactions in the adolescent cortex.

Dr. Cecilia Flores is a Full Professor in the Department of Psychiatry, and an Associate Member of the Department of Neurology and Neurosurgery, McGill University. She completed post-doctoral studies at Harvard Medical School and the Montreal Neurological Institute at McGill University. She has long been interested in the lasting effects of drugs on the brain. While her early work focused on drug-induced changes of the midbrain dopaminergic system with an emphasis on basic fibroblast growth factor, she soon became interested in the guidance cue netrin-1 and its effects on dopamine system development. Dr. Flores began as an assistant professor at McGill in 2004 and is actively involved in teaching and administrative work within her department and university. She runs an active research laboratory at the Douglas Mental Health University Institute and hold grants from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health, the Canadian Institutes for Health Research (CIHR), the Natural Sciences and Engineering Research Council of Canada (NSERC), Les Fonds de Recherche du Québec-Santé (FRQS), and the Canadian Foundation for Innovation (CFI). Dr. Flores received the Canadian College of Neuropsychopharmacology Young Investigator Award in 2010.

Canadian College of Neuropsychopharmacology “Innovations in Neuropsychopharmacology Research” Award 2019.
Canadian College of Neuropsychopharmacology Young Investigator Award in 2010
2014-2018 FRSQ, Senior Chercheur-Boursier
2009-2013 FRSQ, Junior 2 Chercheur-Boursier
2005-2008 FRSQ, Junior 1 Chercheur-Boursier

Project Manager: Giovanni Hernandez

Research Associate: Dominique Nouel

Postdoctoral Fellows: Daniel Hoops, Philip Vassilev

Graduate Students: Lauren Reynolds, Alice Morgunova, Andrea Pantoja Urbán, Christina Popescu, Jose Maria Restrepo

Liste complète de publications: https://www.floreslab.ca/copia-de-drugs-adolescent-developme

• Cooper HM, Flores C. Mechanisms of cortical development: from the embryo to adulthood. Seminars in Cell and Developmental Biology, Editorial, In Press
• Reynolds LM and Flores C Mesocorticolimbic dopamine pathways across adolescence: diversity in development. Frontiers in Neural Circuits, In Press
• Reynolds LM and Flores C (2021). Adolescent dopamine development: connecting experience with vulnerability or resilience to psychiatric disease. In The Neuroscience of Development. V. Preedy (ed) Academic Press https://doi.org/10.1016/B978-0-12-817988-8.00026-9
• Morgunova A, Flores C (2021). MicroRNA regulation of prefrontal cortex development and psychiatric risk in adolescence. Seminars in Cell and Developmental Biology, Online ahead of print PMID: 33933350 *Special issue on Cortical Development: from Embryo to Adolescence
• Morgunova A, Flores C (2021). MicroRNAs as Promising Peripheral Sensors of Prefrontal Cortex Developmental Trajectory and Psychiatric Risk. Neuropsychopharmacology, https://doi.org/10.1038/s41386-021-01113-3 *Invited review for the Hot Topics section in the issue: The Prefrontal Cortex
• Torres-Berrío A, Morgunova A, Giroux M, Cuesta S, Nestler EJ, Flores C (2021). miR-218 in Adolescence Predicts and Mediates Vulnerability to Stress. Biological Psychiatry, 89:911-919 PMID: 33384174 Editor’s choice of Biological Psychiatry’s
• Vassilev P, Pantoja-Urbán AH, Giroux M, Nouel D, Hernandez G, Orsini T, Flores C (2021). Unique effects of social defeat stress in adolescent male mice on the Netrin-1/DCC pathway, prefrontal cortex dopamine and cognition. eNeuro, 8(2):ENEURO.0045-21.2021 PMID: 33619036 *Included on the eNeuro Featured Research page
• Morgunova A, Pokhvisneva I, Nolvi S, Entringer S, Wadhwa P, Gilmore J, Styner M, Buss S, Britto Sassi R, Hall G, O’Donnell KJ, Meaney MJ, Silveira PP, Flores C (2020). DCC gene network in the prefrontal cortex is associated with total brain volume in community-based samples of children. Journal of Psychiatry and Neuroscience, 46(1):E154-E163 PMID: 33206040  (Invited manuscript as recipient of the CCNP Innovation Research Award)
• Cuesta S, Nouel D, Reynolds LM, Morgunova A, Torres-Berrio A, White A, Hernandez G, Cooper HM^, Flores C† (2020). Dopamine Axon Targeting in the Nucleus Accumbens in Adolescence Requires Netrin-1. Frontiers In Cell and Developmental Biology, 8:487 PMID:32714924  Invited Manuscript for a special issue on Development of the Dopaminergic System – From Stem Cells to Circuits
• Vassilev P, Salim M, Popescu C, Flores C, Hernandez G (2020). Low-cost conditioned place preference setup including video recording and analysis of behaviour. MethodsX, 7:100899 PMID: 32405466
• Cuesta S, Restrepo-Lozano JM, Popescu C, He S, Reynolds LM, Israel S, Hernandez G, Rais R, Slusher BS, Flores C (2020). DCC-related developmental effects of abused- versus therapeutic-like amphetamine doses in adolescence. Addiction Biology, 25(4):e12791 PMID: 31192517
• Torres-Berrío A, Nouel D, Cuesta S, Parise EM, Restrepo-Lozano JM, Larochelle P, Nestler EJ, Flores C (2020). miR-218: a molecular switch and potential biomarker of resilience to stress. Molecular Psychiatry, 25:951-964 PMID: 30980043. This article was published in a special issue (Collection)  “Advances in research on stress and behavior” and a was mentioned in the introductory commentary by the Editor
• Torres-Berrio A, Hernandez G, Nestler EJ, Flores C (2020). The Netrin-1/DCC Guidance Cue Pathway as a Molecular Target in Depression: Translational Evidence. Biological Psychiatry, 88(8):611-624 PMID: 32593422 Invited article for a special issue on Depression: Novel Mechanisms and Personalized Treatments. Featured on the cover of Biological Psychiatry, volume 88, issue 8, October 2020
• Vosberg D, Leyton M, Flores C (2020). The Netrin-1/DCC Guidance System: Dopamine Pathway Maturation and Psychiatric Disorders Emerging in Adolescence. Molecular Psychiatry, 25(2):297-307 PMID: 31659271
• Vosberg DE, Beaulé V, Torres-Berrio A, Cooke D, Chalupa A, Jaworska N, Cox SML, Larcher K, Zhang Y, Allard D, Durand F, Dagher A, Benkelfat C, Srour M, Tampieri D, La Piana R, Joober R, Lepore F, Rouleau G, Pascual-Leone A, Fox M, Flores C, Leyton M, Theoret H (2019). Neural function in DCC mutation carriers with and without mirror movements. Annals of Neurology, 85(3):433-442 PMID: 30666715
• Reynolds LM, Flores C (2019). Guidance Cues: Linking Drug Use in Adolescence with Psychiatric Disorders. Neuropsychopharmacology 44 (1):225–226 PMID: 30275561
• Torres-Berrío A, Morgunova A, Giroux M, Cuesta S, Nestler EJ, Flores C. miR-218 in adolescence predicts and mediates vulnerability to stress. Biological Psychiatry, DOI: https://doi.org/10.1016/j.biopsych.2020.10.015 | Cliquer ici pour le text intégral.
• Reynolds LM, Flores C (2019) Guidance Cues: Linking Drug Use in Adolescence with Psychiatric Disorders. Neuropsychopharmacology 44 (1):225–226  PMID:30275561
• Cuesta S, Nouel D, Reynolds LM, Morgunova A, Torres-Berrio A, White A, Hernandez G, Cooper HM, Flores C (2020). Dopamine Axon Targeting in the Nucleus Accumbens in Adolescence Requires Netrin-1. Frontiers In Cell and Developmental Biology, In Press. doi:10.3389/fcell.2020.00487
• Vosberg DE, Leyton M, Flores C. The Netrin-1/DCC guidance system: dopamine pathway maturation and psychiatric disorders emerging in adolescence. Mol Psychiatry. 2019 Oct 28;10.1038/s41380-019-0561-7. doi: 10.1038/s41380-019-0561-7. [Epub ahead of print]. PMID: 31659271.
• Cuesta S, Restrepo-Lozano JM, Popescu C, He S, Reynolds LM, Israel S, Hernandez G, Rais R, Slusher BS, Flores C. DCC-related developmental effects of abused- versus therapeutic-like amphetamine doses in adolescence. Addict Biol. 2019 Jun 13;e12791. doi: 10.1111/adb.12791. [Epub ahead of print]. PMID: 31192517.
• Torres-Berrío A, Nouel D, Cuesta S, Parise EM, Restrepo-Lozano JM, Larochelle P, Nestler EJ, Flores C. MiR-218: a molecular switch and potential biomarker of susceptibility to stress. Mol Psychiatry. 2020 May;25(5):951-964. doi: 10.1038/s41380-019-0421-5. Epub 2019 Apr 12. PMID: 30980043; PMCID: PMC679016.
• Vosberg DE, Beaulé V, Torres-Berrío A, Cooke D, Chalupa A, Jaworska N, Cox SML, Larcher K, Zhang Y, Allard D, Durand F, Dagher A, Benkelfat C, Srour M, Tampieri D, La Piana R, Joober R, Lepore F, Rouleau G, Pascual-Leone A, Fox MD, Flores C, Leyton M, Théoret H. Neural function in DCC mutation carriers with and without mirror movements. Ann Neurol. 2019 Mar;85(3):433-442. doi: 10.1002/ana.25418. Epub 2019 Feb 4. PMID: 30666715; PMCID: PMC6444183.
• Reynolds LM, Yetnikoff L, Pokinko M, Wodzinski M, Epelbaum JG, Lambert LC, Cossette MP, Arvanitogiannis A, Flores, C. Early adolescence is a critical period for the maturation of inhibitory behavior. Cerebral Cortex. 2018;29(9):3676–3686. doi:10.1093/cercor/bhy247
• Vosberg D, Zhang Y, Menegaux A, Chalupa A, Manitt C, Zehntner S, Eng C, DeDuck K, Allard D, Durand F, Dagher A, Benkelfat C, Srour M, Joober R, Lepore F, Rouleau G, Théoret H, Bedell B, Flores C, Leyton M. (2018) Mesocorticolimbic Connectivity and Volumetric Alterations in DCC Mutation Carriers. The Journal of Neuroscience, 38(20):4655-4665
• Hoops D, Reynolds LM Restrepo-Lozano J-M*, Flores C. (2018) Dopamine development in the mouse orbital prefrontal cortex is protracted and sensitive to amphetamine in adolescence. eNeuro, 5(1) ENEURO.0372-17.2017
• Cuesta S, Restrepo J-M, Silvestrin S, Nouel D, Torres-Berrio A, Reynolds LM, Arvanitogiannis A, Flores C. (2018) Non-Contingent Exposure to Amphetamine in Adolescence Recruits miR-218 to Regulate Dcc Expression in the VTA. Neuropsychopharmacology, 43:900-911,
• Reynolds LM, Pokinko M, Torres-Berrio A, Cuesta S, Lambert LC, Del Cid Pellitero E, Wodzinski M, Manitt C, Krimpenfort P, Kolb B, Flores C. (2018) DCC receptors drive prefrontal cortex maturation by determining dopamine axon targeting in adolescence. Biological Psychiatry, 83(2):161-192
• Hoops D, Flores, C. (2017) Making dopamine connections in adolescence. Trends in Neuroscience 40: 709-719
• Walker D, Bell M, Flores C, Gulley J, Willing J, Paul M. (2017) Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos. Journal of Neuroscience 37(45):10855-10866
• Salameh S, Nouel D, Hoops D, Flores C. (2017) An optimized immunohistochemistry protocol for detecting the guidance cue Netrin-1 in neural tissue. MethodsX, 5:1-7
• Madularu D, Mathieu AP, Reynolds LM, Flores C, Rajah MN. (2017) A non-invasive restraining system for awake mouse imaging: assessment of motion. Journal of Neuroscience Methods, 287:53-57
• Pokinko M, Grant A, Shahabi F, Dumont Y, Manitt C, Flores C. (2017) Dcc Haploinsufficiency Regulates Dopamine Receptor Expression Across Postnatal Lifespan. Neuroscience, 346:182-189
• Torres-Berrío A, Lopez JP, Bagot R, Nouel D, Dal-Bo G, Cuesta S, Zhu L, Manitt C, Eng C, Cooper H, Storch F, Turecki G, Nestler E, Flores C. (2017) DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218. Biological Psychiatry, 81(4):306-315
• Reynolds LM, Gifuni A, McCrea T, Shizgal P, Flores C. (2016) dcc haploinsufficiency results in blunted sensitivity to cocaine enhancement of reward seeking Behavioural Brain Research 298(Pt A):27-31
• Verwey M, Grant A, Meti N, Adye-White L, Torres-Berrío A, Rioux V, Lévesque M, Charron F, Flores C (2016) Mesocortical Dopamine Phenotypes in Mice Lacking the Sonic Hedgehog Receptor Cdon. eNeuro, 3(3): ENEURO.0009-16.2016
• Pokinko M, Moquin L, Torres-Berrio A, Gratton A, Flores C. (2015) Resilience to amphetamine in mouse models of netrin-1 haploinsufficiency: role of mesocortical dopamine. Psychopharmacology 20:3719-29
• Reynolds L, Gifuni A, McCrea T, Shizgal P, Flores C. (2015) dcc haploinsufficiency results in blunted sensitivity to cocaine enhancement of reward seeking Behavioural Brain Research S0166-4328(15)00349-6
• Reynolds LM, Makowski CS, Yogendran SV, Kiessling S, Cermakian N, Flores C. (2015) Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a dcc-dependent manner. Neuropsychopharmacology 40: 1101-1112
• Grant A, Manitt C, Flores C. (2014) Haloperidol treatment downregulates DCC expression in the ventral tegmental area. Neuroscience Letters 575: 58-62
• Yetnikoff L, Pokinko M, Arvanitogiannis, Flores C. (2014) Adolescence: A Time of transition for the phenotype of dcc heterozygous mice. Psychopharmacology. 231(8): 1705-14.
• Manitt C*, Eng C*, Pokinko M, Ryan R, Torres-Berrío A, Lopez JP, Yogendran S, Daubaras M, Grant A, Schmidt E, Tronche F, Krimpenfort P, Cooper H, Pasterkamp J, Kolb B, Turecki G, Wong TP, Nestler E, Giros B, Flores C. (2013) dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients. Translational Psychiatry 3:e338.
  *contributed equally to this work
• Auger M, Schmidt E, Manitt C, Dal-Bo G, Pasterkamp J, Flores C. (2013) unc5c haploinsufficient phenotype: striking similarities with the dcc haploinsufficient model. European Journal of Neuroscience 38:2853-2863
• Grant A, Fathalli F, Rouleau G, Joober R, Flores C. (2012) Association between schizophrenia and genetic variations in DCC: a case-control study. Schizophrenia Research. 137: 26-31.
• Manitt C, Mimee A, Eng C, Pokinko M, Stroh T, Cooper HM, Kolb B, and Flores C. (2011) The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry. Journal of Neuroscience 31(23): 8381-8394.
• Flores C. (2011) Role of netrin-1 in the organization of the mesocorticolimbic dopamine system. Journal of Psychiatry and Neuroscience. 36(5): 296-310.
• Manitt C*, Labelle-Dumais C*, Eng C, Grant A, Mimee A, Stroh T, Flores C. (2010) Peri-pubertal emergence of UNC-5 homologue expression by dopamine neurons in rodents. PLoS One 5(7): e11463 *contributed equally to this work
• Yetnikoff L, Eng C, Benning S, Flores C. (2010) Netrin1 receptor in the ventral tegmental area is required for sensitization to amphetamine. European Journal of Neuroscience 31: 1292-1302
• Grant A, Hoops D, Labelle-Dumais C, Prevost M, Rajabi H, Kolb B, Stewart J, Arvanitogiannis A Flores C. (2007) Netrin-1 receptor-deficient mice show enhanced mesocortical dopamine transmission and blunted behavioural responses to amphetamine European Journal of Neuroscience 26:3215-3228
• Flores C, Manitt C, Rodaros D, Thompson KM, Rajabi H, Luk K, Tritsch N., Sadikot A, Stewart J, Kennedy TE (2005) Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine. Molecular Psychiatry 10: 606-612
• Flores C and Coyle JT (2003) Regulation of glutamate carboxypeptidase II function in corticolimbic regions of rat brain by phencyclidine, haloperidol, and clozapine. Neuropsychopharmacology, 28: 1227-1243
• Flores C and Stewart J. (2000) Basic fibroblast growth factor as a mediator of the effects of glutamate in the development of long-lasting sensitization to stimulant drugs: studies in the rat. Psychopharmacology, 151: 152-165