Magnesium deficiency induces anxiety and HPA axis dysregulation: Modulation by therapeutic drug treatment

NEUROPHARMACOLOGY

卷:62

Article

Sartori, S. B.¹ 

[1] Univ Innsbruck, Dept Pharmacol & Toxicol, Inst Pharm, A-6020 Innsbruck, Austria

关键词: Magnesium;    Anxiety;    Stress axis;    Selective serotonin re-uptake inhibitor;    Diazepam;    Corticotropin releasing hormone;    ACTH;    Desipramine;   

DOI  :  10.1016/j.neuropharm.2011.07.027

来源: Elsevier

【 摘 要 】

Preclinical and some clinical studies suggest a relationship between perturbation in magnesium (Mg2+) homeostasis and pathological anxiety, although the underlying mechanisms remain largely unknown. Since there is evidence that Mg2+ modulates the hypothalamic-pituitary adrenal (HPA) axis, we tested whether enhanced anxiety-like behaviour can be reliably elicited by dietary Mg2+ deficiency and whether Mg2+ deficiency is associated With altered HPA axis function. Compared with controls, Mg2+ deficient mice did indeed display enhanced anxiety-related behaviour in a battery of established anxiety tests. The enhanced anxiety-related behaviour of Mg2+ deficient mice was sensitive to chronic desipramine treatment in the hyponeophagia test and to acute diazepam treatment in the open arm exposure test. Mg2+ deficiency caused an increase in the transcription of the corticotropin releasing hormone in the paraventricular hypothalamic nucleus (PVN), and elevated ACTH plasma levels, pointing to an enhanced set-point of the HPA axis. Chronic treatment with desipramine reversed the identified abnormalities of the stress axis. Functional mapping of neuronal activity using c-Fos revealed hyperexcitability in the PVN of anxious Mg2+ deficient mice and its normalisation through diazepam treatment. Overall, the present findings demonstrate the robustness and validity of the Mg2+ deficiency model as a mouse model of enhanced anxiety, showing sensitivity to treatment with anxiolytics and antidepressants. It is further suggested that dysregulations in the HPA axis may contribute to the hyper-emotionality in response to dietary induced hypomagnesaemia. This article is part of a Special Issue entitled 'Anxiety and Depression'. (C) 2011 Elsevier Ltd. All rights reserved.

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