The goal of my lab is to understand how mood is regulated. Specifically, we aim to identify the molecular mechanisms and neural circuits that modulate anxiety and depression using mouse models. One major focus of the lab is to identify the neurobiological mechanisms underlying the antidepressant response. All current antidepressant treatments increase synaptic monoamines within minutes to hours, but the onset of therapeutic effects requires chronic administration (2-4 weeks). Therefore, fast-onset antidepressants are a major unmet need. Our lab has developed novel mouse models in which mice exhibit behavioral responses that emerge during chronic, but not short-term, antidepressant treatment. Using these models, we are uncovering the neural mechanisms underlying classical antidepressants, and identifying novel putative fast-onset antidepressants. Another major area of our research is to identify biological mechanisms underlying anxiety disorders such as Obsessive Compulsive Disorder (OCD). We have developed a mouse pharmacological model of aspects of OCD. We are also studying genes identified as “hits” in large-scale genome-wide association studies for OCD to determine how they contribute to OCD-related behaviors in mice. A third major area of research in the lab is dissecting the neural control of activity-based anorexia (ABA). Rodents exposed to scheduled feeding or running wheels adapt to their environment and maintain normal bodyweight. However, rodents subjected to both conditions develop profound hyperactivity, reduced voluntary food intake, and weight loss. This paradigm provides a model for aspects of Anorexia Nervosa and related disorders. We are dissecting the neural circuits, molecules, and receptors which regulate the ABA phenomenon. All of the projects in the lab use a combination of behavioral, molecular, genetic, and pharmacological techniques.
1. Serotonin 2C receptor antagonists induce fast-onset antidepressant effects. MD Opal, SJ Klenotich, M Morais, J Bessa, J Winkle, D Doukas, L Kay, N Sousa, SC Dulawa. Molecular Psychiatry. 2013 Oct 29. doi: 10.1038/mp.2013.144.
2. Gestational environment programs adult depression-like behavior through methylation of the calcitonin gene-related peptide gene. J Jiao, MD Opal, SC Dulawa. Molecular Psychiatry 18:1273-80, 2013.
3. Expression of the G72/G30 gene in transgenic mice induces behavioral changes. L Cheng, E Hattori, A Nakajima, NA Shanahan, MD Opal, C Zhang, SC Dulawa, Y Tang, ES Gershon C Liu. Molecular Psychiatry 19:175-83, 2014.
4. Olanzapine, but not fluoxetine, treatment increases survival in activity-based anorexia in mice. SJ Klenotich, MP Seiglie, MS McMurray, JD Roitman, D Le Grange, P Dugad, SC Dulawa. Neuropsychopharmacology 37:1620-31, 2012.
5. Essential role for orbitofrontal 5-HT1B receptors in obsessive-compulsive disorder-like behavior and serotonin reuptake inhibitor response in mice. NA Shanahan, LP Velez, VL Masten, SC Dulawa. Biological Psychiatry 70:1039-48, 2011.
Antidepressant response to chronic citalopram treatment in eight inbred mouse strains. J Jiao, AM Nitzke, DG Doukas, MP Seiglie, SC Dulawa. Psychopharmacology 213:509-20, 2011.
Murine Warriors or Worriers: the Saga of Comt1, B2 SINE Elements and the Future of Translational Genetics. AA Palmer, SC Dulawa. Frontiers in Neuroscience 4:177, 2010.
8. Chronic reductions in serotonin transporter function prevent 5-HT1B-induced behavioral effects in mice. NA Shanahan, KA Holick, VL Masten, C Waeber, M Ansorge, JA Gingrich, MA Geyer, R Hen, SC Dulawa. Biological Psychiatry 65:401-8, 2009.
9. Assessing the validity of current mouse genetic models of obsessive compulsive disorder. L Wang, HB Simpson, SC Dulawa. Behavioural Pharmacology 20:119-33, 2009.
10. Behavioral effects of chronic fluoxetine in BALB/cJ mice do not require adult hippocampal neurogenesis or the serotonin 1A receptor. KA Holick, DC Lee, R Hen, SC Dulawa. Neuropsychopharmacology 33:406-417, 2008.