Altered protein kinase a in brain of learned helpless rats: effects of acute and repeated stress.

Abstract:

BACKGROUND:Stress-induced learned helplessness (LH) in animals serves as a model of behavioral depression and some aspects of posttraumatic stress disorder. We examined whether LH behavior is associated with alterations in protein kinase A (PKA), a critical phosphorylating enzyme, how long these alterations persist after inescapable shock (IS), and whether repetition of IS prolongs the duration of LH behavior and changes in PKA. METHODS:Rats were exposed to IS either on day 1 or twice, on day 1 and day 7. Rats were tested for escape latency on days 2 and 4 after day 1 IS or days 2, 8, and 14 after day 1 and day 7 IS. [(3)H]cAMP (cyclic adenosine monophosphate) binding, catalytic activity and expression of PKA subunits were determined in frontal cortex and hippocampus. RESULTS:Higher escape latencies were observed in rats tested on day 2 after single IS and on day 14 after repeated IS. Concurrently, reduced [(3)H]cAMP binding, PKA activity, and expression of selective PKA RIIbeta and Calpha and Cbeta subunits were observed in the brains of these rats. CONCLUSIONS:Repeated IS prolongs the duration of LH behavior, and LH behavior is associated with reductions in apparent activity and expression of PKA. These reductions in PKA may be critical in the pathophysiology of depression and other stress-related disorders.

journal_name

Biol Psychiatry

journal_title

Biological psychiatry

authors

Dwivedi Y,Mondal AC,Shukla PK,Rizavi HS,Lyons J

doi

10.1016/j.biopsych.2004.03.018

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

30-40

issue

1

eissn

0006-3223

issn

1873-2402

pii

S0006322304004494

journal_volume

56

pub_type

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