Congenitally learned helpless rats show abnormalities in intracellular signaling

• Published in: Biological psychiatry (1969) Vol. 53; no. 6; pp. 520 - 529
• Main Authors: Kohen, Ruth, Neumaier, John F, Hamblin, Mark W, Edwards, Emmeline
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.03.2003; Elsevier Science
• Subjects: Adult and adolescent clinical studies; animal models; Animals; Biological and medical sciences; Brain - metabolism; Brain - physiopathology; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Depression; DNA Primers - genetics; gene expression; Gene Expression - genetics; Genes, bcl-2 - genetics; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Helplessness, Learned; Hippocampus - metabolism; Hippocampus - physiopathology; learned helplessness; Male; Medical sciences; Mood disorders; Mood Disorders - genetics; Mood Disorders - metabolism; Mood Disorders - physiopathology; Polymerase Chain Reaction; Protein Kinase C - metabolism; Protein Kinase C-epsilon; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Sprague-Dawley; RNA, Messenger - genetics; Second Messenger Systems - physiology; second messengers; Signal Transduction - physiology; Depression; animal models; second messengers; mood disorders; learned helplessness; gene expression; Mood disorder; Animal model; Rat; Enzyme; Pathogenesis; Transferases; Rodentia; Male; Prefrontal cortex; Gene expression; Case study; Binding protein; Vertebrata; Mammalia; Protein kinase; Animal; Genetics; Reverse transcription polymerase chain reaction; Hippocampus
• ISSN: 0006-3223; 1873-2402
• DOI: 10.1016/S0006-3223(02)01503-2

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. 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. 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 3β, and protein kinase C ε. Congenitally learned helpless animals show evidence of altered signal transduction and regulation of apoptosis compared to cNLH and SD control animals.