title: The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2.
abstract: BACKGROUND
  A number of epidemiological studies have established a link between insulin resistance and the prevalence of depression. The occurrence of depression was found to precede the onset of diabetes and was hypothesized to be associated with inherited inter-related insufficiency of the peripheral and central insulin receptors. Recently, dicholine succinate, a sensitizer of the neuronal insulin receptor, was shown to stimulate insulin-dependent H2O2 production of the mitochondrial respiratory chain leading to an enhancement of insulin receptor autophosphorylation in neurons. As such, this mechanism can be a novel target for the elevation of insulin signaling.
  
  
  RESULTS
  Administration of DS (25 mg/kg/day, intraperitoneal) in CD1 mice for 7 days prior to the onset of stress procedure, diminished manifestations of anhedonia defined in a sucrose test and behavioral despair in the forced swim test. Treatment with dicholine succinate reduced the anxiety scores of stressed mice in the dark/light box paradigm, precluded stress-induced decreases of long-term contextual memory in the step-down avoidance test and hippocampal gene expression of IGF2.
  
  
  CONCLUSIONS
  Our data suggest that dicholine succinate has an antidepressant-like effect, which might be mediated via the up-regulation of hippocampal expression of IGF2, and implicate the neuronal insulin receptor in the pathogenesis of stress-induced depressive syndrome.
authors.affiliation: Interdisciplinary Center for Neurosciences, Heidelberg University, and Institute for Neuroanatomy, University Clinic Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Cline
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Dmitry
authors.initials: D
authors.lastname: Malin
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Revishchin
authors.forename: Galia V
authors.initials: GV
authors.lastname: Pavlova
authors.forename: Raymond
authors.initials: R
authors.lastname: Cespuglio
authors.forename: Tatyana
authors.initials: T
authors.lastname: Strekalova
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001007:Anxiety / Q000150:complications / Q000188:drug therapy / Q000523:psychology; D003863:Depression / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology / Q000627:therapeutic use; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000502:physiology*; D008297:Male; D008569:Memory Disorders / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D013390:Succinylcholine / Q000494:pharmacology / Q000627:therapeutic use*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; C513121:IGF2 protein, mouse; D007335:Insulin-Like Growth Factor II; D011972:Receptor, Insulin; D013390:Succinylcholine; D007099:Imipramine