The proposed project will examine effects of a number of drugs supplied by GlaxoSmithKline, assessing these drugs for their potential antidepressant capability. Assessment will be made primarily using two new animal models. One of these is a new screening technique for effective antidepressant treatments that appears to be more selective for detecting effective antidepressant drugs than is previously-developed screening techniques. This model uses a selectively-bred line of rats, the Swim-test Susceptible rat (or Susceptible rat), that shows heightened vulnerability to having its active behavior in a swim test reduced when it is exposed to a mild stress situation prior to the swim test. Chronic treatment with antidepressant drugs has been found to block this vulnerability; chronic treatment with other psychoactive drugs is without effect. Thus, this test appears usable to detect antidepressant drugs, and to discriminate these from other psychoactive drugs. The second model is a new rodent model of depression in which the animals show long-lasting symptoms of depression (i.e., 20-35 days duration) following a single exposure to a stressful situation. In previously-existing rodent models, depression-like symptoms have been transitory (i.e., lasted 2-4 days); thus, previous models did not allow drugs to be administered after onset of depressive symptoms so that recovery could be observed as it occurs in humans. This new model permits this to be done. The model in which long-lasting symptoms occur uses another selectively-bred rat- the Hyperactive rat. In addition to testing of drugs in these models, drugs also will be tested in a standard Porsolt swim test. Finally, additional development of animal models is proposed. In this regard, we will (a) attempt to further perfect the Hyperactive rat as a potential model for study of bipolar disorder, and (b) subject our selectively-bred rats to maternal separation as a possible means of producing improved models of affective disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19MH069056-04
Application #
7553546
Study Section
Special Emphasis Panel (ZMH1)
Project Start
Project End
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2006
Total Cost
$289,399
Indirect Cost
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Hodgins, Gabrielle E; Blommel, Jared G; Dunlop, Boadie W et al. (2018) Placebo Effects Across Self-Report, Clinician Rating, and Objective Performance Tasks Among Women With Post-Traumatic Stress Disorder: Investigation of Placebo Response in a Pharmacological Treatment Study of Post-Traumatic Stress Disorder. J Clin Psychopharmacol 38:200-206
Pape, Julius C; Carrillo-Roa, Tania; Rothbaum, Barbara O et al. (2018) DNA methylation levels are associated with CRF1 receptor antagonist treatment outcome in women with post-traumatic stress disorder. Clin Epigenetics 10:136
Dunlop, Boadie W; Binder, Elisabeth B; Iosifescu, Dan et al. (2017) Corticotropin-Releasing Factor Receptor 1 Antagonism Is Ineffective for Women With Posttraumatic Stress Disorder. Biol Psychiatry 82:866-874
Maples-Keller, Jessica L; Price, Matthew; Rauch, Sheila et al. (2017) Investigating Relationships Between PTSD Symptom Clusters Within Virtual Reality Exposure Therapy for OEF/OIF Veterans. Behav Ther 48:147-155
Guo, Ji-Dong; O'Flaherty, Brendan M; Rainnie, Donald G (2017) Serotonin gating of cortical and thalamic glutamate inputs onto principal neurons of the basolateral amygdala. Neuropharmacology 126:224-232
Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose et al. (2016) Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy. Behav Res Ther 82:28-37
Price, Matthew; Maples, Jessica L; Jovanovic, Tanja et al. (2015) An investigation of outcome expectancies as a predictor of treatment response for combat veterans with PTSD: comparison of clinician, self-report, and biological measures. Depress Anxiety 32:392-9
Grillon, Christian; Hale, Elizabeth; Lieberman, Lynne et al. (2015) The CRH1 antagonist GSK561679 increases human fear but not anxiety as assessed by startle. Neuropsychopharmacology 40:1064-71
Ridgewell, Caitlin; Bray, Allison; Curtis, Kaylah et al. (2015) Enhanced Olfactory Cortex Connectivity in a Patient With PTSD With Olfactory Hallucinations. J Neuropsychiatry Clin Neurosci 27:e170-1
Stehouwer, Jeffrey S; Bourke, Chase H; Owens, Michael J et al. (2015) Synthesis, binding affinity, radiolabeling, and microPET evaluation of 4-(2-substituted-4-substituted)-8-(dialkylamino)-6-methyl-1-substituted-3,4-dihydropyrido[2,3-b]pyrazin-2(1H)-ones as ligands for brain corticotropin-releasing factor type-1 (CRF1) rec Bioorg Med Chem Lett 25:5111-4

Showing the most recent 10 out of 57 publications