CLINICAL STUDIES OF DEPLETION OF ZINC IN ASSOCIATION WITH CENTRAL NERVOUS SYSTEM DISORDERS

Pol J Pharmacol. 2002 Nov-Dec;54(6):587-92.

Mechanisms contributing to antidepressant zinc actions.

Nowak G, Szewczyk B.

Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 3 1-343 Krakow, Poland.

Zinc is a trace element, which is an important modulator of mammalian nervous and immune systems. Its deficiency is related to human depression. Our recent data indicate involvement of zinc in the mechanism of antidepressant treatment. Moreover, zinc exhibits antidepressant-like effects in animal models of depression in rodents. Since zinc also enhances antidepressant effect in laboratory animals, its potential therapeutic value in human depression is under evaluation. This article reviews the alterations in central and peripheral zinc homeostasis in relation to pathophysiology and treatment of depression.

PMID: 12866713 [PubMed - indexed for MEDLINE]

J Affect Disord. 1994 Jun;31(2):135-40.

Hypozincemia in depression.

Maes M, D'Haese PC, Scharpe S, D'Hondt P, Cosyns P, De Broe ME.

Department of Psychiatry, Case Western Reserve University, Cleveland, OH.

This study investigates serum levels of zinc in 48 unipolar depressed subjects (16 minor, 14 simple major and 18 melancholic subjects) and 32 normal volunteers, and the relationships between zincemia and plasma neopterin levels, postdexamethasone adrenocorticotropic hormone and cortisol values, and anorexia-weight loss. Serum zinc levels were significantly lower in major depressed subjects than in normal controls, whereas minor depressed subjects showed intermediate values. There were significant negative correlations between serum zinc, and severity of depression and plasma neopterin concentrations. No significant relationships between zincemia and either postdexamethasone hormone values or anorexia/weight loss were found. The findings suggest that hypozincemia in major depression may be related to activation of cell-mediated immunity in that illness.

PMID: 8071476 [PubMed - indexed for MEDLINE]

Acta Psychiatr Scand. 1990 Dec;82(6):451-3.

Zinc in depressive disorder.

McLoughlin IJ, Hodge JS.

Department of Psychiatry, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom.

Plasma zinc levels were measured in 14 patients with primary affective disorder on admission to hospital; they were compared with plasma zinc levels in group of 14 age- and sex-matched controls. A significant difference in zinc levels was found between the 2 groups. Plasma zinc levels of 9 of the depressed patients on admission to hospital and at the point of discharge were compared; a significant increase in zinc levels was detected.

PMID: 2291414 [PubMed - indexed for MEDLINE]

Clinical studies using Zinc to study antidepressant-like effects in animals

Behav Brain Res. 2003 Sep 15;144(1-2):87-93.

Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice.

Rosa AO, Lin J, Calixto JB, Santos AR, Rodrigues AL.

Departamento de Bioquimica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario, Trindade, Florianopolis 88040-900, SC, Brazil.

This study investigated the involvement of NMDA receptors and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like effects of zinc in the forced swimming test (FST). The immobility times in the FST and in the tail suspension test (TST) were reduced by zinc chloride (ZnCl(2), 30 and 10-30 mg/kg intraperitoneal (i.p.), respectively). The doses active in the FST and TST reduced locomotor activity in an open-field. The antidepressant-like effect of ZnCl(2) in the FST was prevented by pre-treatment of animals with guanosine 5'-monophosphate (GMP), ascorbic acid, L-arginine, or S-nitroso-N-acetyl-penicillamine (SNAP), but not with D-arginine, administered at doses that per se produced no anti-immobility effect. The immobility time of mice treated with ZnCl(2)+MK-801 was not different from the result obtained with ZnCl(2) or MK-801 alone, but ZnCl(2)+imipramine had a greater effect in the FST than administration of either drug alone. Pre-treatment of animals with a sub-threshold dose of ZnCl(2) prevented the anti-immobility effect of MK-801, ketamine, GMP, L-arginine or N(G)-nitro-L-arginine (L-NNA), but did not alter the effect of imipramine or fluoxetine. Taken together, the results demonstrate that zinc produced an antidepressant-like effect that seems to be mediated through its interaction with NMDA receptors and the L-arginine-NO pathway.

PMID: 12946598 [PubMed - indexed for MEDLINE]

Brain Res Bull. 2003 Jul 15;61(2):159-64.

Antidepressant-like effects of acute and chronic treatment with zinc in forced swim test and olfactory bulbectomy model in rats.

Nowak G, Szewczyk B, Wieronska JM, Branski P, Palucha A, Pilc A, Sadlik K, Piekoszewski W.

Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Krakow, Poland. nowak@if-pan.krakow.pl

The activity of zinc administered intraperitoneally, acutely (in single dose), sub-chronically (in triple doses) or chronically (once daily for 14 days) were assessed in the forced swim test (FST) and olfactory bulbectomy (OB) model of depression in rats. Previously, we have demonstrated that acute administration of zinc sulfate is active in FST in rats and mice. In the present study, zinc hydroaspartate in a dose of 65 mg/kg (11.5 mgZn/kg), all: acute, sub-chronic and chronic administration, reduced the immobility time in the FST in rats. Removal of olfactory bulbs (OB surgery) in rats is associated with variety of behavioral abnormalities such as deficit in a step-down passive avoidance or hyperactivity in the "open field" test. Both acute and chronic administration of zinc hydroaspartate reduced the number of trials needed to the learning passive avoidance and reduced the OB-induced hyperactivity in rats. At the time schedule following zinc hydroaspartate administration, when behavioral experiments were performed, the serum zinc concentrations were significantly higher than control-physiological values. These results confirm activity of zinc in the FST, show its antidepressant-like activity in the OB rat model of depression, demonstrate the lack of tolerance to these effects and suggest relationship of these antidepressant-like effects with the rise in serum zinc. These animal data further suggest antidepressant activity of zinc in human depression.

PMID: 12832002 [PubMed - indexed for MEDLINE]

Brain Res Bull. 2001 May 15;55(2):297-300.

Antidepressant-like properties of zinc in rodent forced swim test.

Kroczka B, Branski P, Palucha A, Pilc A, Nowak G.

Department of Neurobiology, Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

The effects of zinc, the N-methyl-D-aspartate glutamate receptor inhibitor, were studied in mice and rats using the forced swim test. Zinc (ZnSO4) in a dose of 30 mg/kg and imipramine (30 mg/kg), reduced the immobility time in the forced swim test in both species. Moreover, combined treatment in this test with zinc and imipramine at their ineffective doses (1 and 5 mg/kg, respectively) induced a statistically significant effect in rats. The doses active in the forced swim test reduced (in mice) or did not affect (in rats) locomotor activity. The results obtained indicate that zinc induces an antidepressant-like effect and enhances the effect of imipramine in the forced swim test, suggesting a potential antidepressant activity of zinc in humans.

PMID: 11470330 [PubMed - indexed for MEDLINE]

Pol J Pharmacol. 2000 Sep-Oct;52(5):403-6.

Zinc exhibits an antidepressant-like effect in the forced swimming test in mice.

Kroczka B, Zieba A, Dudek D, Pilc A, Nowak G.

Department of Neurobiology, Polish Academy of Sciences, Krakow, Poland.

The effects of zinc, the NMDA receptor inhibitor, were studied in the forced swimming (Porsolt's) test in mice. Zinc (ZnSO4) at a dose of 30 mg/kg (but not at a dose of 10 mg/kg), similarly to imipramine (30 mg/kg), reduced the immobility time in that test. Moreover, zinc at both doses reduced the locomotor activity. The obtained results indicate that zinc induces an antidepressant-like effect in the forced swimming test. Since zinc reduces the locomotor activity, this antidepressant-like effect is not related to the alteration of general activity.

PMID: 11334234 [PubMed - indexed for MEDLINE]