Specific creatine rise in learned helplessness induced by electroconvulsive shock treatment

Abstract

Metabolic changes in the hippocampus formation can be investigated with in vivo magnetic resonance spectroscopy (MRS). Learned helplessness (LH) is a well validated animal model of depression which we established in Sprague-Dawley rats defining some as "learned helpless" (LH) or not "learned helpless" (NLH). Helpless and non-helpless rats received a course of daily administered electroconvulsive shocks (ECS) for 6 days. MRS measurements were performed on a 4.7 T animal scanner with an average voxel size within the rat hippocampus of 10 microl. In LH rats hippocampal creatine/NAA rose significantly (14%) whereas creatine/NAA of NLH rats showed no increase at all. A possible connection between hippocampal creatine levels and major depressive disorders as a reflection of changes in energy metabolism is discussed.

Effects of Depressive-Like Behavior of Rats on Brain Glutamate Uptake

“…We used a LH paradigm protocol well established in neurobiological research on molecular pathogenesis and therapy of depression and encompasses good construct and face validity [56][57][58]. The protocol enable to identify individual animals with LH for subsequent neurobiological studies and compare them with selected animals displaying most pronounced not helpless behavior.…”

Stress models of depression: Forming genetically vulnerable strains

“…Learned helpless animals have been found to be responsive to all these medications with a 3-5 day delay in onset (Henn et al, 2002;Malberg and Duman, 2003;Sartorius et al, 2003;Sherman et al, 1982;Takamori et al, 2001). Benzodiazepines have been found to prevent the acquisition of learned helplessness (Paul, 1988).…”

Reduced Expression of GABA Transporter GAT3 in Helpless Rats, an Animal Model of Depression

“…This model has first been described by Seligman et al [49] and extended by Sherman et al [50]. It is well established in neurobiological research on the molecular pathogenesis and therapy of depression and encompasses good construct and face validity, reflecting the polygenetic basis of genetic transmission, and responds to antidepressant therapy [51][52][53]. Depression-like behaviour is induced through exposure to uncontrollable and unpredictable aversive events, and strains transmitting the vulnerability for helplessness on a genetic basis have been established by selective breeding [54,55].…”