Cecilia Flores PhD
6875 Boulevard LaSalle
Researcher, Douglas Research Centre
Full Professor, Department of Psychiatry, McGill University
Associate Member, Department of Neurology and Neurosurgery, McGill University
Adolescent brain development and susceptibility to psychopathology
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.
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. [Epub ahead of print] https://doi.org/10.1016/j.biopsych.2020.04.025
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
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
The laboratory of Cecilia Flores has an opening position for a postdoctoral fellow. The research project is funded by the National Institute on Drug Abuse (NIDA), and concerns cellular and molecular mechanisms by which drugs of abuse in adolescence disrupt brain development. This position is for a highly motivated individual with experience in neurodevelopmental biology and/or neuroanatomy and microscopy. Experience in behavioral testing in rodents is desirable. Applicants should have a PhD in neuroscience or neurobiology and a strong publication record.
Interested individuals should send a curriculum vitae and the names/e-mails/phone numbers of three people who could provide letters of reference by email to email@example.com.
For additional information please visit our webpage http://ceciliafloreslab.com
The laboratory of Cecilia Flores at McGill University (Department of Psychiatry) has an opening position for a graduate student. The project concerns cellular and molecular processes underlying adolescent brain development and how drugs of abuse and stressors disrupt these events. This position is for a highly motivated individual with experience in molecular biology and neuroscience. Experience in behavioral testing in rodents is desirable, but not required. Applicants should have a BSc or MSc in neuroscience or neurobiology and a strong academic record.
Interested individuals should send a curriculum vitae, a copy of their transcripts, and the names/e-mails/phone numbers of three people who could provide letters of reference by email to firstname.lastname@example.org.
For additional information please visit our webpage http://ceciliafloreslab.com
DCC-related developmental effects of abused- versus therapeutic-like amphetamine doses in adolescence. Addict Biol. 2019:e12791.
MiR-218: a molecular switch and potential biomarker of susceptibility to stress. Mol Psychiatry. 2019.
Neural function in DCC mutation carriers with and without mirror movements. Ann Neurol. 2019;85(3):433-442.
Mesocorticolimbic Connectivity and Volumetric Alterations in Mutation Carriers. J Neurosci. 2018;38(20):4655-4665.
Non-Contingent Exposure to Amphetamine in Adolescence Recruits miR-218 to Regulate Dcc Expression in the VTA. Neuropsychopharmacology. 2018;43(4):900-911.
Adolescence and Reward: Making Sense of Neural and Behavioral Changes Amid the Chaos. J Neurosci. 2017;37(45):10855-10866.
Making Dopamine Connections in Adolescence. Trends Neurosci. 2017;40(12):709-719.
A non-invasive restraining system for awake mouse imaging. J Neurosci Methods. 2017;287:53-57.
Dcc haploinsufficiency regulates dopamine receptor expression across postnatal lifespan. Neuroscience. 2017;346:182-189.
DCC Confers Susceptibility to Depression-like Behaviors in Humans and Mice and Is Regulated by miR-218. Biol Psychiatry. 2017;81(4):306-315.
Making Dopamine Connections in Adolescence. Trends in Neurosciences. 2017;In Press.
dcc Haploinsufficiency results in blunted sensitivity to cocaine enhancement of reward seeking. Behav Brain Res. 2016;298(Pt A):27-31.
Resilience to amphetamine in mouse models of netrin-1 haploinsufficiency: role of mesocortical dopamine. Psychopharmacology (Berl). 2015;232(20):3719-29.
Amphetamine in adolescence disrupts the development of medial prefrontal cortex dopamine connectivity in a DCC-dependent manner. Neuropsychopharmacology. 2015;40(5):1101-12.
The Netrin-1 receptor DCC is a regulator of maladaptive responses to chronic morphine administration. BMC Genomics. 2014;15:345.
Haloperidol treatment downregulates DCC expression in the ventral tegmental area. Neurosci Lett. 2014;575:58-62.
Target-dependent expression of the netrin-1 receptor, UNC5C, in projection neurons of the ventral tegmental area. Neuroscience. 2014;260:36-46.
Adolescence: a time of transition for the phenotype of dcc heterozygous mice. Psychopharmacology (Berl). 2014;231(8):1705-14.
dcc orchestrates the development of the prefrontal cortex during adolescence and is altered in psychiatric patients. Transl Psychiatry. 2013;3:e338.
Association between schizophrenia and genetic variation in DCC: a case-control study. Schizophr Res. 2012;137(1-3):26-31.
The netrin receptor DCC is required in the pubertal organization of mesocortical dopamine circuitry. J Neurosci. 2011;31(23):8381-94.
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