Hoops D, Kyne RF, Schatz KC, Li P, Salameh S, Ewing E, He A, Orsini T, Durand D, Giroux M, Hernandez G, Popescu C, Liu G, Paul MJ, Flores C. The scheduling of adolescence with Netrin-1 and UNC5c. bioRxiv 2023.01.19.521267; doi: https://doi.org/10.1101/2023.01.19.521267
Darcq E, Nouel D*, Hernandez G*, Pokinko M*, Ash P, Moquin L, Gratton A, Kieffer B, Flores C
(2022). Reduced dopamine release in Dcc haploinsufficiency mice protects against the
rewarding effects of stimulant drugs, but not for morphine and ethanol.
Psychopharmacology. (Invited manuscript for Special Issue of Psychopharmacology to honor the contributions of Dr. Nadia Chaudhri to addiction research and society at large)
Reynolds, L. M., Hernandez, G., Popescu, C., MacGowan, D., Nouel, D., Cuesta, S., Burke, S., Savell, K., Zhao, J., Restrepo-Lozano, J. M., Pokinko, M., Giroux, M., Israel, S., Orsini, T., He, S., Wodzinski, M., Epelbaum, J. G., Trudeau, L.-E., Kolb, B., Flores, C. (2022). Amphetamine disrupts dopamine axon growth in adolescence by a sex-specific mechanism. BioRxiv. https://doi.org/10.1101/2022.12.14.520468, Preprint
Reynolds, L.M., Pantoja-Urbán, A.H., MacGowan, D., Manitt, C., Nouel, D., Flores, C. (2023). Quantifying Dopaminergic Innervation in Rodents Using Unbiased Stereology. In: Fuentealba-Evans, J.A., Henny, P. (eds) Dopaminergic System Function and Dysfunction: Experimental Approaches. Neuromethods, vol 193. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2799-0_2
Restrepo-Lozano JM, Flores C, Silveira PP (2022) Novel functional genomic approaches bridging psychiatry and neuroscience. Biological Psychiatry: Global Open Science, In Press
Restrepo-Lozano JM, Pokhvisneva I, Wang Z, Patel S, Meaney MJ, Silveira PP, Flores C. (2022) Corticolimbic DCC gene co-expression networks as predictors of impulsivity in children. Molecular Psychiatry. April 7:1-9. doi: 10.1038/s41380-022-01533-7, PMID: 35388180.
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Vassilev P, Fonseca E, Hernandez G, Pantoja-Urbán AH, Giroux M, Nouel D, Van Leer E, Flores C. (2022) Custom-built operant conditioning setup for calcium imaging and cognitive testing in freely moving mice. eNeuro 9(1), doi: 10.1523/ENEURO.0430-21.2022, PMID: 35105659
Cooper HM, Flores C. (2021) Mechanisms of cortical development: from the embryo to
adulthood. Seminars in Cell and Developmental Biology 118:1-3, Editorial, PMID: 34462250
Reynolds LM and Flores C (2021). Mesocorticolimbic dopamine pathways across adolescence: diversity in development. Frontiers in Neural Circuits, In Press
Morgunova A, Flores C (2022). MicroRNAs as Promising Peripheral Sensors of Prefrontal Cortex
Developmental Trajectory and Psychiatric Risk. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 47(1), 387-388 PMID: 34312494
*Invited review for the Hot Topics section in the issue: The Prefrontal Cortex
Morgunova A, Flores C (2021). MicroRNA Regulation of Prefrontal Cortex Development and Psychiatric Risk in Adolescence. Seminars in Cell and Developmental Biology, doi.org/10.1016/j.semcdb.2021.04.011
* Special issue on Cortical Development: from Embryo to Adolescence
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
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
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(9):911-919 PMID:33384174
* Editor's choice of that issue
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 childhood. Journal of Psychiatry and Neuroscience 46(1):20008146(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, Invited Manuscript for a special issue on Development of the Dopaminergic System – From Stem Cells to Circuits. doi: 10.3389/fcell.2020.00487. PMID:32714924
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 Oct15;88(8):611-624.
doi: 10.1016/j.biopsych.2020.04.025. PMID:32593422
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 susceptibility to stress. Molecular Psychiatry 25:951-964
Cuesta S, Restrepo JM, Popescu C, He S, Reynolds LM, Israel S, Hernandez G, Rais R, Slusher B, Flores C (2020). DCC-related developmental effects of abused- versus therapeutic-like amphetamine doses in adolescence.
Addiction Biology 25(4):e12791 doi: 10.1111/adb.12791. PMID:31192517
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 Apr 25;7:100899. doi:10.1016/j.mex.2020.100899. PMID:32405466
Vosgerg D, Leyton M, Flores C. (2020) The Netrin-1/DCC Guidance System: Dopamine Pathway Maturation and Psychiatric Disorders Emerging in Adolescence.
Molecular Psychiatry Feb;25(2):297-307. doi:10.1038/s41380-019-0561-7. 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 MD, Flores C, Leyton M, Theoret H. (2019) Neural function in DCC mutation carriers with and without mirror movements. Annals of Neurology 85:433-442
Reynolds LM, Flores C. (2019) Guidance Cues: Linking Drug Use in Adoescence with Psychiatric Disorders.
Neuropsychopharmacology 44(1):225-226
Reynolds LM, Yetnikoff L, Pokinko M, Wodzinski M, Epelbaum JG, Lambert LC, Cossette MP, Arvanitogiannis A, Flores C. (2018) Early adolescence is a critical period for the maturation of inhibitory behavior.
Cerebral Cortex 29(9):3676-3686
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.
Journal of Neuroscience 38(20):4655-4665
* McGill Newsroom
* Research featured by Society for Neuroscience
* Research featured by EurekaAlert
* Research featured by MedicalXpress
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):181-192
* Research referenced by LaPresse+ (French)
* Research referenced by CBC News
* Referenced by National Institute of Drug Abuse
* Research referenced by Maman Pour La Vie (French)
* Science Highlight on National Institute on Drug Abuse website
* 2018 recipient of McGill MedStar Award
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
Salameh S, Nouel D, Flores C, Hoops D. (2017) An optimized immunohistochemistry protocol for detecting the guidance cue Netrin-1 in neural tissue.
MethodsX 5:1-7
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
Hoops D, Flores C (2017). Making dopamine connections in adolescence.
Trends in Neurosciences 40: 709-719
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 RC, Nouel D, Dal-Bo G, Cuesta S, Zhu L, Manitt C, Eng C, Cooper H, Storch F, Turecki G, Nestler EJ, 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
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 Jul 13;3(3)
Reynolds LM, Gifuni AJ, McCrea ET, Shizgal P, Flores C. (2016) dcc haploinsufficiency results in blunted sensitivity to cocaine enhancement of reward seeking.
Behavioural Brain Research 298(A): 27–31 Invited Submission to Special Issue: Developmental Regulation of Memory in Anxiety and Addiction
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 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
*Referenced by National Institute of Drug Abuse
Grant A, Manitt C, Flores C. (2014) Haloperidol treatment downregulates DCC expression in the ventral tegmental area.
Neuroscience Letters 575: 58-62
Liang D-Y, Zheng M, Sun Y, Sahbaie P, Low S.A, Peltz G, Scherrer G, Flores C, Clark D. (2014) The Netrin-1 Receptor DCC is a Regulator of Maladaptive Responses to Chronic Morphine Administration. BMC Genomics 15:345.
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.
Daubaras M, Dal-Bo G, Flores C. (2013) Target-dependent expression of the netrin-1 receptor, UNC5C, in projection neurons of the ventral tegmental area.
Neuroscience 260C:36-46.
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
This article was featured on the Canadian National News Network (CTV). It was also covered by Douglas Hospital News, ABC2News, the Boston Globe, Global News, Healthline News, Wired, Genetic Engineering & Biotechnology
News, Medical Daily, Top News Arab Emirates, and Mental Health
Kim J, Lavan D, Chen N, Flores C, Cooper H, Lawrence A. (2013) Netrin-1 receptor-deficient mice show age-specific impairment in drug-induced locomotor hyperactivity but still self-administer methamphetamine. Psychopharmacology 230:607-616
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
Aguilar-Valles A, Jung S, Poole S, Flores, C, Luheshi G. (2012) Leptin and interleukin-6 alter the development of mesolimbic dopamine neurons in a model of prenatal inflammation in rat. Psychoneuroendocrinology. 37(7): 956-969.
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.
Argento J, Arvanitogiannis A, Flores C. (2012) Juvenile Exposure to Methylphenidate Reduces Cocaine Reward and Alters Netrin-1 Receptor Expression in Adulthood.
Behavioural Brain Research. 229(1): 202-207.
Flores C. (2011) Role of netrin-1 in the organization of the mesocorticolimbic dopamine system. Journal of Psychiatry and Neuroscience. 36(5): 296-310.
Yetnikoff L, Almey MA, Arvanitogiannis A, Flores C. (2011) Abolition of the behavioral phenotype of adult netrin-1 receptor deficient mice by exposure to amphetamine during the juvenile period. Psychopharmacology 217: 505-514.
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.
*see This Week in The Journal section for commentary
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
Aguilar-Valles A, Flores, C, Luheshi G. (2010) Prenatal inflammation-induced hypoferremia alters dopamine function in the offspring. PLoS One 5(6): e10967
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, Speed Z, Labelle-Dumais C, Flores C. (2009) Post-pubertal emergence of a dopaminergic phenotype in netrin-1 receptor deficient mice.
European Journal of Neuroscience 30: 1318-1328
Hercher C, Parent M, Flores C, Canetti L, Mechawar N, Turecki G. (2009) An alcohol-related increase of glia cell density in the anterior cingulated cortex of suicides.
Journal of Psychiatry and Neuroscience 34: 281-288
Flores C, Bhardwaj S K, Labelle-Dumais C, Srivastava L. (2009) Altered netrin-1 receptor expression in dopamine terminal regions following neonatal ventral hippocampal lesions in the rat. Synapse 63: 54-60
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
Yetnikoff L, Labelle-Dumais C, Flores C. (2007) Regulation of netrin-1 receptors by amphetamine in the adult brain. Neuroscience 150:764-773
Flores C, Wen X, Labelle-Dumais C, Kolb B. (2007) Chronic phencyclidine treatment increases dendritic spine density in prefrontal cortex and nucleus accumbens neurons.
Synapse 61:978-984
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, Stewart J, Salmaso N, Zhang Y, Boksa P. (2002) Astrocytic basic fibroblast growth factor expression in dopaminergic regions after perinatal anoxia.
Biological Psychiatry, 52: 362-370
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
Flores C and Stewart J. (2000) Changes in astrocytic basic fibroblast growth factor expression during and after prolonged exposure to escalating doses of amphetamine.
Neuroscience, 98: 287-293>
Flores C, Samaha, A-N, & Stewart J. (2000) Requirement of endogenous basic fibroblast growth factor for sensitization to amphetamine.
Journal of Neuroscience, 20: RC7 (1-5)
Flores C., Salmaso, N., Cain, S., Rodaros, D. & Stewart J. (1999) Ovariectomy of adult rats leads to increased expression of astrocytic basic fibroblast growth factor in the ventral tegmental area and in dopaminergic projection regions of the entorhinal and prefrontal cortex.
Journal of Neuroscience, 19: 8665-8673
Flores C., Rodaros D., & Stewart J. (1998) Long-lasting induction of astrocytic basic fibroblast growth factor by repeated injections of amphetamine: blockade by concurrent treatment with a glutamate antagonist. Journal of Neuroscience, 18: 9547-9555