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Neural Plasticity
Volume 2016, Article ID 5098591, 17 pages
http://dx.doi.org/10.1155/2016/5098591
Research Article

Individual Differences in Behavioural Despair Predict Brain GSK-3beta Expression in Mice: The Power of a Modified Swim Test

1Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, 6229 ER Maastricht, Netherlands
2Laboratory of Biomolecular Screening, Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnii Proezd 1, Chernogolovka, Moscow 142432, Russia
3Laboratory of Cognitive Dysfunctions, Institute of General Pathology and Pathophysiology, Baltiiskaya Street 8, Moscow 125315, Russia
4Department of Physiology, Federal State Budgetary Scientific Institution “Institute of Experimental Medicine”, Akademika Pavlova Street 12, Saint-Petersburg 197022, Russia
5Department of Human Anatomy, I.M. Sechenov First Moscow State Medical University, Mokhovaya Street 11-10, Moscow 125009, Russia
6Division of Molecular Psychiatry, Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080 Wuerzburg, Germany

Received 15 February 2016; Revised 9 May 2016; Accepted 18 May 2016

Academic Editor: Divya Mehta

Copyright © 2016 Tatyana Strekalova et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

While deficient brain plasticity is a well-established pathophysiologic feature of depression, little is known about disorder-associated enhanced cognitive processing. Here, we studied a novel mouse paradigm that potentially models augmented learning of adverse memories during development of a depressive-like state. We used a modification of the classic two-day protocol of a mouse Porsolt test with an additional session occurring on Day 5 following the initial exposure. Unexpectedly, floating behaviour and brain glycogen synthase kinase-3 beta (GSK-3beta) mRNA levels, a factor of synaptic plasticity as well as a marker of distress and depression, were increased during the additional swimming session that was prevented by imipramine. Observed increases of GSK-3beta mRNA in prefrontal cortex during delayed testing session correlated with individual parameters of behavioural despair that was not found in the classic Porsolt test. Repeated swim exposure was accompanied by a lower pGSK-3beta/GSK-3beta ratio. A replacement of the second or the final swim sessions with exposure to the context of testing resulted in increased GSK-3beta mRNA level similar to the effects of swimming, while exclusion of the second testing prevented these changes. Together, our findings implicate the activation of brain GSK-3beta expression in enhanced contextual conditioning of adverse memories, which is associated with an individual susceptibility to a depressive syndrome.