Trehalose induced antidepressant-like effects and autophagy enhancement in mice

N. Z. Kara, L. Toker, G. Agam, Grant W Anderson, R. H. Belmaker, H. Einat

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Rationale: The disaccharide trehalose protects cells from hypoxic and anoxic injury and suppresses protein aggregation. In vivo studies with trehalose show cellular and behavioral beneficial effects in animal models of neurodegenerative diseases. Moreover, trehalose was shown to enhance autophagy, a process that had been recently suggested to be involved in the therapeutic action of antidepressant and mood-stabilizing drugs. Objective: The present study was therefore designed to explore antidepressant and mood-stabilizing activity of trehalose in animal models for depression and mania. Methods: Trehalose 1 or 2 % was administered for 3 weeks as a drinking solution to Black Swiss mice (a model of manic-like behaviors) or 2 % to ICR mice and their behavior evaluated in a number of tests related to depression or mania. The effects of trehalose were compared with similar chronic administration of the disaccharide maltose as well as with a vehicle (water) control. Results: Chronic administration of trehalose resulted in a reduction of frontal cortex p62/beclin-1 ratio suggesting enhancement of autophagy. Trehalose had no mood-stabilizing effects on manic-like behavior in Black Swiss mice but instead augmented amphetamine-induced hyperactivity, an effect similar to antidepressant drugs. In ICR mice, trehalose did not alter spontaneous activity or amphetamine-induced hyperactivity but in two separate experiments had a significant effect to reduce immobility in the forced swim test, a standard screening test for antidepressant-like effects. Conclusions: The results suggest that trehalose may have antidepressant-like properties. It is hypothesized that these behavioral changes could be related to trehalose effects to enhance autophagy.

Original languageEnglish (US)
Pages (from-to)367-375
Number of pages9
Issue number2
StatePublished - Sep 2013

Bibliographical note

Funding Information:
Acknowledgments The study was partially supported by a grant from the United States–Israel Binational Science Foundation to Haim Einat and Grant W Anderson (grant # 2011313). The authors would like to thank the Endowment for Medical Research (Huston, TX) for their generous donation of trehalose. We would also like to thank Dr. Shlomit Flaisher-Grinberg, Ms. Sara Schuster, Ms. Keren Raphael, and Mr. Jesse Juetten for their technical assistance.


  • Animal models
  • Autophagy
  • Bipolar disorder
  • Cellular plasticity
  • Depression


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