(provided by candidate): The bed nucleus of the stria terminalis (BNST) is believed to mediate anxiety-like states produced by exposure to uncontrollable, unpredictable, and/or chronic stress. These stressors are associated with long-term elevations in serotonergic (5-HT) and corticosterone release. Many individual BNST neurons exhibit both a 5-HT1A-mediated, anxiolytic, hyperpolarization and a 5-HT2-mediated, anxiogenic, depolarization in response to exogenous 5-HT application. The net response of each cell thus depends on the balance of these two responses. Chronic corticosterone has been shown to decrease 5-HT1A function and increase 5- HT2 function in several brain areas. This action within the BNST should shift the balance of 5-HT responses to favor more 5-HT2-mediated depolarizations, which, when combined with increased 5-HT release, could mediate anxiety.
The specific aims i n this proposal are designed to determine whether chronic corticosterone shifts the electrophysiological response of BNST neurons to favor 5-HT2-mediated function, and whether chronic corticosterone produces a more anxiogenic behavioral profile to BNST 5-HT. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32MH072088-02
Application #
6958549
Study Section
Special Emphasis Panel (ZRG1-F02A (20))
Program Officer
Curvey, Mary F
Project Start
2004-11-16
Project End
2006-07-31
Budget Start
2005-11-16
Budget End
2006-07-31
Support Year
2
Fiscal Year
2006
Total Cost
$37,882
Indirect Cost
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Missig, Galen; Mei, Linda; Vizzard, Margaret A et al. (2017) Parabrachial Pituitary Adenylate Cyclase-Activating Polypeptide Activation of Amygdala Endosomal Extracellular Signal-Regulated Kinase Signaling Regulates the Emotional Component of Pain. Biol Psychiatry 81:671-682
Hammack, Sayamwong E; May, Victor (2015) Pituitary adenylate cyclase activating polypeptide in stress-related disorders: data convergence from animal and human studies. Biol Psychiatry 78:167-77
Kocho-Schellenberg, Margaret; Lezak, Kimberly R; Harris, Olivia M et al. (2014) PACAP in the BNST produces anorexia and weight loss in male and female rats. Neuropsychopharmacology 39:1614-23
Lezak, Kimberly R; Roman, Carolyn W; Braas, Karen M et al. (2014) Regulation of bed nucleus of the stria terminalis PACAP expression by stress and corticosterone. J Mol Neurosci 54:477-84
Hammack, Sayamwong E; Roman, Carolyn W; Lezak, Kimberly R et al. (2010) Roles for pituitary adenylate cyclase-activating peptide (PACAP) expression and signaling in the bed nucleus of the stria terminalis (BNST) in mediating the behavioral consequences of chronic stress. J Mol Neurosci 42:327-40
Guo, J-D; Hammack, S E; Hazra, R et al. (2009) Bi-directional modulation of bed nucleus of stria terminalis neurons by 5-HT: molecular expression and functional properties of excitatory 5-HT receptor subtypes. Neuroscience 164:1776-93
Hammack, Sayamwong E; Mania, Irakli; Rainnie, Donald G (2007) Differential expression of intrinsic membrane currents in defined cell types of the anterolateral bed nucleus of the stria terminalis. J Neurophysiol 98:638-56