Open Access Highly Accessed Research article

The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2

Brandon H Cline1, Harry WM Steinbusch2, Dmitry Malin34, Alexander V Revishchin45, Galia V Pavlova5, Raymond Cespuglio6 and Tatyana Strekalova2*

Author affiliations

1 Interdisciplinary Center for Neurosciences, Heidelberg University, and Institute for Neuroanatomy, University Clinic Heidelberg, Im Neuenheimer Feld 307, 69120, Heidelberg, Germany

2 School for Mental Health and Neuroscience, Department of Neuroscience, Maastricht University, Universiteitssingel 40, NL, 6229 ER, Maastricht, Netherlands

3 University of Wisconsin, Carbon Cancer Center, WIMR 3016, 1111 Highland Ave, Madison, WI, 53705, USA

4 Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaya str. 8, 125315, Moscow, Russia

5 Institute of Gene Biology of Russian Academy of Sciences, 34/5 Vavilov str, Moscow, 119334, Russia

6 Claude Bernard University, Lyon1, Faculty of Medicine, EA 4170, Av. Rockefeller 8, 69373, Lyon, CEDEX 08, France

For all author emails, please log on.

Citation and License

BMC Neuroscience 2012, 13:110  doi:10.1186/1471-2202-13-110

Published: 18 September 2012



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.


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.


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.

Dicholine succinate; Insulin-like receptor; Insulin growth factor 2; Hippocampus; Stress-induced anhedonia; Mouse