Altered protein kinase a in brain of learned helpless rats: effects of acute and repeated stress.
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.
Dwivedi
Yogesh
Y
Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois, USA.
Mondal
Amal C
AC
Shukla
Pradeep K
PK
Rizavi
Hooriyah S
HS
Lyons
Jennifer
J
D000818:Animals; D003345:Corticosterone / Q000097:blood; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D004924:Escape Reaction; D005625:Frontal Lobe / Q000201:enzymology* / Q000503:physiopathology; D006380:Helplessness, Learned; D006624:Hippocampus / Q000201:enzymology* / Q000503:physiopathology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D013315:Stress, Psychological / Q000097:blood / Q000201:enzymology* / Q000503:physiopathology
D007527:Isoenzymes; D012333:RNA, Messenger; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D003345:Corticosterone