Zinc deficiency induces enhanced depression-like behaviour and altered limbic activation reversed by antidepressant treatment in mice.
A relationship between zinc (Zn)-deficiency and mood disorders has been suspected. Here we examined for the first time whether experimentally-induced Zn-deficiency in mice would alter depression- and anxiety-related behaviour assessed in established tests and whether these alterations would be sensitive to antidepressant treatment. Mice receiving a Zn-deficient diet (40% of daily requirement) had similar homecage and open field activity compared to normally fed mice, but displayed enhanced depression-like behaviour in both the forced swim and tail suspension tests which was reversed by chronic desipramine treatment. An anxiogenic effect of Zn-deficiency prevented by chronic desipramine and Hypericum perforatum treatment was observed in the novelty suppressed feeding test, but not in other anxiety tests performed. Zn-deficient mice showed exaggerated stress-evoked immediate-early gene expression in the amygdala which was normalised following DMI treatment. Taken together these data support the link between low Zn levels and depression-like behaviour and suggest experimentally-induced Zn deficiency as a putative model of depression in mice.
Whittle
N
N
Department of Pharmacology and Toxicology, Institute of Pharmacy, Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innsbruck, Austria.
Lubec
G
G
Singewald
N
N
D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D008032:Limbic System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D015032:Zinc / Q000172:deficiency*
D000928:Antidepressive Agents; D015032:Zinc