Lab webpage

Animal models of psychiatric disorders

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. We are pursuing this goal by studying the neurobiological mechanisms underlying the antidepressant response. Although antidepressant treatment increases synaptic monoamines within minutes to hours, the therapeutic effects of antidepressants require chronic administration (weeks) to emerge. This delay suggests that long-term adaptive changes to chronic antidepressant treatment mediate the therapeutic response, although the mechanisms underlying this effect have not been determined.  One substantial barrier to elucidating the mechanisms underlying the antidepressant response has been a lack of animal models that are sensitive to the chronic effects of antidepressants. Our lab has developed novel animal models in which mice exhibit behavioral responses following chronic, but not short-term, antidepressant treatment. To dissect the mechanisms underlying the behavioral responses to chronic antidepressant treatment, we use a combination of molecular, genetic engineering (including tTA/tetO inducible gene expression systems), and pharmacological techniques. We are currently using these techniques to study the role of a number of molecules, including elements of the serotonin system. We are also exploring early environmental factors that regulate anxiety and depression, and the response to antidepressants.

References

SC Dulawa, R Hen, K Scearce-Levie, MA Geyer. Serotonin1B receptor modulation of startle reactivity, habituation, and prepulse inhibition in wild type and serotonin1B knockout mice. Psychopharmacology 132:125-134; 1997.  R Grailhe, C Waeber, SC Dulawa, JP Hornung, X Zhuang, D Brunner, MA Geyer, R Hen. Increased exploratory activity in mice lacking the 5-HT5A receptor. Neuron 22:581-91; 1999.  SC Dulawa, DK Grandy, MJ Low, MP Paulus, MA Geyer. Dopamine D4 receptor-knockout mice exhibit reduced exploration of novel stimuli. Journal of Neuroscience 19:9550-9556; 1999.  SC Dulawa, C Gross, K Stark, R Hen, MA Geyer. Knockout mice reveal opposite roles for 5-HT1A and 1B receptors in prepulse inhibition. Neuropsychopharmacology 22:650-659; 2000.  SC Dulawa, K Scearce-Levie, R Hen, MA Geyer. Serotonin releasers increase prepulse inhibition in serotonin 1B knockout mice. Psychopharmacology 149:306-312; 2000.  SC Dulawa, MA Geyer. Phenotypic differences and the effects of serotonergic agents on prepulse inhibition and habituation in three mouse strains. Neuropharmacology 39:2170-2179; 2000.  SA Henry, SC Dulawa, MA Geyer, F Conquet. Assessment of a prepulse inhibition deficit in a mutant mouse lacking Mglu5 receptors. Molecular Psychiatry 9:35-41; 2004.  SC Dulawa, KA Holick, B Gundersen, R Hen. Effects of chronic fluoxetine in animal models of anxiety and depression. Neuropsychopharmacology 29:1321-30; 2004.  MT Englander, SC Dulawa, P Bhansali, C Schmauss. How stress and fluoxetine modulate serotonin 2C receptor pre-mRNA editing. Journal of Neuroscience  25(3):648-51, 2005.  SC Dulawa, R Hen. Recent developments in animal models of the antidepressant response: the novelty-Induced hypophagia test. Neurosci Biobehav Rev 29(4-5):771-783, 2005.

Last updated 08/06/06