Congenitally learned helpless rats show abnormalities in intracellular signaling.
BACKGROUND
Affective disorders and the drugs used to treat them lead to changes in intracellular signaling. We used a genetic animal model to investigate to what extent changes in intracellular signal transduction confer a vulnerability to mood or anxiety disorders.


METHODS
Levels of gene expression in a selectively bred strain of rats with a high vulnerability to develop congenitally learned helplessness (cLH), a strain highly resistant to the same behavior (cNLH) and outbred Sprague-Dawley (SD) control animals were compared using quantitative reverse transcription polymerase chain reaction.


RESULTS
Congenitally learned helpless animals had a 24%-30% reduced expression of the cyclic adenosine monophosphate response element binding protein messenger ribonucleic acid (mRNA) in the hippocampus and a 40%-41% increased level of the antiapoptotic protein bcl-2 mRNA in the prefrontal cortex compared to cNLH and SD rats. Other significant changes included changes in the expression levels of the alpha catalytic subunit of protein kinase A, glycogen synthase kinase 3beta, and protein kinase C epsilon.


CONCLUSIONS
Congenitally learned helpless animals show evidence of altered signal transduction and regulation of apoptosis compared to cNLH and SD control animals.
Kohen
Ruth
R
Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA.
Neumaier
John F
JF
Hamblin
Mark W
MW
Edwards
Emmeline
E
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000235:genetics; D019254:Genes, bcl-2 / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006380:Helplessness, Learned; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019964:Mood Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000378:metabolism; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D017931:DNA Primers; D012333:RNA, Messenger; D000242:Cyclic AMP; C497257:Prkce protein, rat; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon; D038362:Glycogen Synthase Kinase 3