Zinc deficiency induces enhanced depression-like behaviour and altered limbic activation reversed by antidepressant treatment in mice

• Published in: Amino acids Vol. 36; no. 1; pp. 147 - 158
• Main Authors: Whittle, N, Lubec, G, Singewald, N
• Format: Journal Article
• Language: English
• Published: Vienna Vienna : Springer Vienna 2009; Springer Vienna; Springer Nature B.V
• Subjects: Analytical Chemistry; Animals; Antidepressants; Antidepressive Agents - therapeutic use; Behavior, Animal - drug effects; Biochemical Engineering; Biochemistry; Biomedical and Life Sciences; Body Weight - drug effects; Depression - drug therapy; Depression - metabolism; Hypericum perforatum; Life Sciences; Limbic System - drug effects; Limbic System - metabolism; Limbic System - physiology; Limbic System - physiopathology; Male; Mice; Mice, Inbred C57BL; Motor Activity - drug effects; Neurobiology; Original Article; Proteomics; Zinc; Zinc - deficiency; NMDA; Immediate-early gene Zif268; Depression; Light/dark test; Elevated plus maze; Brain zinc
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-008-0195-6

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.