6875 Boulevard Lasalle
Professor in the Department of Psychiatry
Associate Member of the Department of Neurology and Neurosurgery
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.
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 an Associate 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.
The 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
Research Associate: Dr. Dominique Nouel
Research Assistant: Mathew Pokinko
Postdoctoral Fellows: Dr. Michael Verwey and Dr. Santiago Cuesta
PhD Students: Lauren Reynolds, Angelica Torres-Berrio, and Daniel Vosberg
Undergraduate Students: Jose Maria Restrepo, Daniel Kapustin, Laura Lambert, Laurence Guindon Carrier
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 firstname.lastname@example.org.
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 email@example.com.
For additional information please visit our webpage http://ceciliafloreslab.com
In the news
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.
A non-invasive restraining system for awake mouse imaging. J Neurosci Methods. 2017;287:53-57.
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.
Abolition of the behavioral phenotype of adult netrin-1 receptor deficient mice by exposure to amphetamine during the juvenile period. Psychopharmacology (Berl). 2011;217(4):505-14.
Peri-pubertal emergence of UNC-5 homologue expression by dopamine neurons in rodents. PLoS ONE. 2010;5(7):e11463.
Netrin-1 receptor-deficient mice show enhanced mesocortical dopamine transmission and blunted behavioural responses to amphetamine. Eur J Neurosci. 2007;26(11):3215-28.