Candice Contet, PhD
Scripps Research Joint Appointments
Research Focus
The Contet laboratory investigates the molecular mechanisms mediating the behavioral effects of alcohol, with a focus on neuroadaptations driving excessive alcohol drinking. A first aspect of our research focuses on known molecular targets of alcohol, such as GIRK and BK channels, two potassium channels that can be activated by alcohol in vitro. Our goal is to assess the in vivo relevance of alcohol's action on these proteins by evaluating their contribution to acute intoxication, tolerance, voluntary drinking and dependence. A second aspect of our research explores the neurocircuitry mediating the role of the neuropeptide CRF in the transition to alcohol dependence and in the symptomatology of alcohol withdrawal. This work involves a combination of histological, electrophysiological and behavioral studies. Finally, we are undertaking exploratory projects, which aim to identify novel genes contributing to or protecting from excessive drinking.
To achieve these goals, we use validated mouse models of differential alcohol intake, in combination with a variety of genetic tools, such as knockout and transgenic mice, as well as viral vectors. We are also providing other investigators with validated tools to manipulate gene expression in rodents through TSRI Alcohol Research Center Viral Vector Core.
Ultimately, our hope is to curb the devastating impact of alcoholism and drug addiction on individuals, their family and the community as a whole, through the identification of vulnerable populations and the development of better treatments. If you share our dedication to this goal, you can help our research by making a donation to the Pearson Center. Your support will make a difference.
Education
Ph.D., University of Strasbourg, 2006Professional Experience
2016-2017 Associate Professor, Committee on the Neurobiology of Addictive Disorders (CNAD), Scripps Research2008-2016 Assistant Professor, Committee on the Neurobiology of Addictive Disorders (CNAD), Scripps Research
Awards & Professional Activities
2010: Travel award from the National Institute on Alcohol Abuse and Alcoholism to attend the International Society for Biomedical Research on Alcoholism Congress in Paris, France2006-2007: Postdoctoral fellowship (Fondation pour la Recherche Médicale)
2002-2005: PhD fellowship, coupled to teaching duties (French Research Ministry)
2005: Travel award from the Federation of European Neuroscience Societies to attend the 35th Annual Meeting of the American Society for Neuroscience in Washington DC, USA
2005: Travel award from the International Narcotics Research Conference to attend the NIDA "Frontiers of Addiction" Mini-Convention in Washington DC, USA
1998-2002: Pregraduate fellowship, as a civil servant trainee at École Normale Supérieure
Selected References
Verheij MM, Vendruscolo LF, Caffino L, Giannotti G, Cazorla M, Fumagalli F, Riva MA, Homberg JR, Koob GF, Contet C (2016) Systemic Delivery of a Brain-Penetrant TrkB Antagonist Reduces Cocaine Self-Administration and Normalizes TrkB Signaling in the Nucleus Accumbens and Prefrontal Cortex. J Neurosci 36(31):8149-59.
Herman MA, Contet C, Roberto M (2016) A functional switch in tonic GABA currents alters the output of central amygdala CRF receptor-1 neurons following chronic ethanol exposure. J Neurosci, 36(42):10729-10741.
Contet C, Goulding SP, Kuljis DA & Barth AL (2016) BK channels in the central nervous system. In Candice Contet (Ed), Big on BK: Current Insights into the Function of Large Conductance Voltage- and Ca2+- Activated K+ Channels at the Molecular, Cellular, and Systemic Levels. Int Rev Neurobiol, 128:281-342.
Munoz MB, Padgett CL, Rifkin R, Terunuma M, Wickman K, Contet C, Moss SJ, Slesinger PA (2016) A role for the GIRK3 subunit in methamphetamine-induced attenuation of GABAB receptor-activated GIRK currents in VTA dopamine neurons. J Neurosci, 36(11):3106-14.
Herman MA, Sidhu H, Stouffer DG, Kreifeldt M, Le D, Cates-Gatto C, Munoz MB, Roberts AJ, Parsons LH, Roberto M, Wickman K, Slesinger PA, Contet C (2015) GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol. Proc Natl Acad Sci USA, 112(22):7091-6.
Schmeichel BE, Barbier E, Misra KK, Contet C, Schlosburg JE, Grigoriadis D, Williams JP, Karlsson C, Pitcairn C, Heilig M, Koob GF, Vendruscolo LF (2015) Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats. Neuropsychopharmacology, 40(5):1123-9.
Kreifeldt M, Cates-Gatto C, Roberts AJ, Contet C (2015) BK channel β1 subunit contributes to behavioral adaptations elicited by chronic intermittent ethanol exposure. Alcohol Clin Exp Res, 39(12):2394-402.
Cohen A, Whitfield TW, Kreifeldt M, Koebel P, Kieffer BL, Contet C, George O, Koob GF (2014) Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization. PLoS One, 9(5):e97216. Link
Kreifeldt M, Le D, Treistman SN, Koob GF, Contet C (2013) BK channel β1 and β4 auxiliary subunits exert opposite influences on escalated ethanol drinking in dependent mice. Front Integr Neurosci, 7:105. Link
Contet C, Kim A, Le D, Iyengar SK, Kotzebue RW, Yuan CJ, Kieffer BL, Mandyam CD (2013) μ-Opioid receptors mediate the effects of chronic ethanol binge drinking on the hippocampal neurogenic niche. Addict Biol, in press. Link
Herman MA, Contet C, Justice NJ, Vale W, Roberto M (2013). Novel subunit-specific tonic GABA currents and differential effects of ethanol in the central amygdala of CRF receptor-1 reporter mice. J Neurosci, 33(8):3284-98. Link
Contet C (2012) Gene expression under the influence: Transcriptional profiling of ethanol in the brain. Curr Psychopharm, 1(4):301-14. Link
Semenova S, Contet C, Roberts AJ & Markou A (2012) Mice lacking the b4 subunit of the nicotinic acetylcholine receptor show memory deficits, altered anxiety- and depression-like behavior, and diminished nicotine-induced analgesia. Nicotine Tob Res, 14(11):1346-55. Link
Contet C, Gardon O, Filliol D, Becker J, Koob GF & Kieffer BL (2011) Identification of genes regulated in the mouse extended amygdala by excessive ethanol drinking associated with dependence. Addiction Biology, 16(4):615-9. Link
Contet C, Whisler KN, Jarrell H, Kenny PJ & Markou A (2010) Patterns of responding differentiate intravenous nicotine self-administration from responding for a visual stimulus in C57BL/6J mice. Psychopharmacology (Berl), 212(3):283-99. Link
Homberg JR & Contet C (2009) Deciphering the interaction of the corticotropin-releasing factor and serotonin brain systems in anxiety-related disorders. J Neurosci, 29(44):13743-5. NIHMS 163482. Link
Scherrer G, Imamachi N, Cao YQ, Contet C, Mennicken F, O'Donnell D, Kieffer BL & Basbaum AI (2009) Dissociation of the opioid receptor mechanisms that control mechanical and heat pain. Cell, 137(6):1148-59. Link
Contet C, Filliol D, Matifas A & Kieffer BL (2008) Morphine-induced analgesic tolerance, locomotor sensitization and physical dependence do not require modification of m opioid receptor, cdk5 and adenylate cyclase activity. Neuropharmacology, 54(3):475-486. Link
Contet C, Dierich A & Kieffer BL (2007) Knock-in mice reveal nonsense-mediated mRNA decay in the brain. Genesis, 45(1):38-43. Link
Contet C, Gavériaux-Ruff C, Matifas A, Caradec C, Champy M-F & Kieffer BL (2006) Dissociation of analgesic and hormonal responses to forced swim stress using opioid receptor knockout mice. Neuropsychopharmacology, 31(8):1733-1744. Link
Grillet N, Pattyn A, Contet C, Kieffer BL, Goridis C & Brunet JF (2005) Generation and characterization of Rgs4 mutant mice. Mol Cell Biol, 25(10):4221-4228. Link
Contet C, Kieffer BL & Befort K (2004) m opioid receptor: a gateway to drug addiction. Curr Opin Neurobiol, 14(3): 370-378. Link
Contet C, Matifas A & Kieffer BL (2004) No evidence for G-protein-coupled ε receptor in the brain of triple opioid receptor knockout mouse. Eur J Pharmacol, 492(2-3): 131-136. Link
Scherrer G, Befort K, Contet C, Becker J, Matifas A & Kieffer BL (2004) The δ agonists DPDPE and deltorphin II recruit predominantly m receptors to produce thermal analgesia: a parallel study of m, δ and combinatorial opioid receptor knockout mice. Eur J Neurosci, 19(8): 2239-48. Link
Contet C, Rawlins JN & Bannerman DM (2001) Faster is not surer - A comparison of C57BL/6J and 129S2/Sv mouse strains in the watermaze. Behav Brain Res, 125 (1-2): 261-267. Link
Contet C, Rawlins JN & Deacon RM (2001) A comparison of 129S2/SvHsd and C57BL/6JOlaHsd mice on a test battery assessing sensorimotor, affective and cognitive behaviours: implications for the study of genetically modified mice. Behav Brain Res, 124(1): 33-46. Link
Links
Pearson Center for Alcoholism and Addiction Research
Integrative Neuroscience Initiative on Alcoholism (INIA)
Research Society on Alcoholism