The present grant is a revision of a previous proposal, MH45265, whose aim was to elucidate the role of central alpha-l noradrenergic function in stress-induced behavioral dysfunction. The proposal is focussed on a proposed neurobiological pathway by which stress produces behavioral inactivity via a corticosterone-induced desensitization of behaviorally activating brain alpha-1 adrenergic receptors. The proposed studies will further elucidate this pathway by determining: 1) the subtype of brain alpha-1 receptor (1A, 1B or ID) that mediates behavioral activation and whether it is desensitized by stress and corticosterone as preliminary data indicate; 2) the brain region within which it acts to stimulate behavioral activity; 3) the role of endogenous corticosterone and individual corticosteroid receptors in its desensitization by stress; and 4) the role of changes in the density and coupling of this alpha-1 receptor in the mechanism of the desensitization. The proposed studies will yield important clues on the pathophysiology of inactive behavioral states occurring in several psychiatric and stress related disorders and will stimulate clinical research into possible alterations in brain alpha-l receptors that may sensitize individuals to stress-induced behavioral impairment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH045265-13
Application #
6679963
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Winsky, Lois M
Project Start
1989-05-01
Project End
2005-11-30
Budget Start
2003-12-01
Budget End
2005-11-30
Support Year
13
Fiscal Year
2004
Total Cost
$293,207
Indirect Cost
Name
New York University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Lin, Yan; Sarfraz, Yasmeen; Jensen, Ashley et al. (2011) Participation of brainstem monoaminergic nuclei in behavioral depression. Pharmacol Biochem Behav 100:330-9
Lin, Yan; Suckow, Raymond F; Sarfraz, Yasmeen et al. (2011) Further evidence for an immediate antidepressant action of intracerebral drug administration in a model of chronic depression. Int J Neuropsychopharmacol 14:691-6
Stone, Eric A; Lin, Yan; Sarfraz, Yasmeen et al. (2011) The role of the central noradrenergic system in behavioral inhibition. Brain Res Rev 67:193-208
Stone, Eric A; Lin, Yan; Sarfraz, Yasmeen et al. (2011) Antidepressant-like action of intracerebral 6-fluoronorepinephrine, a selective full ?-adrenoceptor agonist. Int J Neuropsychopharmacol 14:319-31
Stone, Eric A; Lin, Yan (2011) Open-space forced swim model of depression for mice. Curr Protoc Neurosci Chapter 9:Unit9.36
(2010) Erratum: Corrigendum to ""Marked behavioral activation from inhibitory stimulation oflocus coeruleus alpha1-adrenoceptors by a full agonist"" Brain Res 1326:193
Stone, Eric A; Lin, Yan; Sarfraz, Yasmeen et al. (2009) Marked behavioral activation from inhibitory stimulation of locus coeruleus alpha1-adrenoceptors by a full agonist. Brain Res 1291:21-31
Lin, Yan; Quartermain, David; Dunn, Adrian J et al. (2008) Possible dopaminergic stimulation of locus coeruleus alpha1-adrenoceptors involved in behavioral activation. Synapse 62:516-23
Stone, Eric A; Lin, Yan (2008) An anti-immobility effect of exogenous corticosterone in mice. Eur J Pharmacol 580:135-42
Stone, Eric A; Lin, Yan; Quartermain, David (2008) A final common pathway for depression? Progress toward a general conceptual framework. Neurosci Biobehav Rev 32:508-24

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