Zinc deficiency induces depression-like symptoms in adult rats.

There is mounting evidence suggesting a link between serum zinc levels and clinical depression. Not only is serum zinc negatively correlated with the severity of symptoms, but zinc levels appear to be lowest in patients who do not respond to antidepressant drug therapy. It is not known if reduced zinc levels are contributing to depression, or the result of dietary or other factors associated with major depression. Thus, we designed this study to test the hypothesis that dietary zinc deficiency would induce depression-like behaviors in rats. Two-month-old male rats were fed zinc adequate (ZA, 30 ppm), deficient (ZD, 1 ppm), or supplemented (ZS, 180 ppm) diets for 3 weeks. Consistent with the development of depression, ZD rats displayed anorexia (p<0.001), anhedonia (reduced saccharin:water intake, p< 0.001), and increased anxiety-like behaviors in a light-dark box test (p<0.05). Furthermore, the antidepressant drug fluoxetine (10 mg/kg body wt) reduced behavioral despair, as measured by the forced swim test, in rats fed the ZA and ZS rats (p<0.05), but was ineffective in ZD rats. Together these studies suggest that zinc deficiency leads to the development of depression-like behaviors that may be refractory to antidepressant treatment.

Regulation of metabolic rate and substrate utilization by zinc deficiency.

The trace metal zinc (Zn) is essential for the catalytic activity of many enzymes involved in energy nutrient metabolism and appears to regulate hormones, such as insulin, leptin, and thyroid hormone that play key roles in metabolism. Thus, this study used the continuous monitoring of oxygen consumption, carbon dioxide production, locomotion, and food intake to determine the effect of dietary Zn restriction on metabolic rate (MR), basal metabolic rate (BMR), and respiratory quotient (RQ). Rats were fed a Zn-adequate (ZA, 28 ppm) or Zn-deficient (ZD, <1 ppm) diet for 8 days, followed by a 4-day refeeding period. To control for reductions in food intake that characteristically occur in ZD rats, an additional group was pair-fed (PF) the same amount ZA food eaten by ZD rats. The mean caloric intake of ZD rats was significantly lower than ZA rats by day 3. By day 8, ZD and PF rats weighed 64% and 67% of ZA rats, respectively, (P <.01). Pair feeding resulted in increased locomotor activity, such that the distance traveled for PF rats (316 +/- 43 m) was 6 times that of ZA (53 +/- 6 m). Despite the fact that PF and ZD rats had the same food intake, there was no increase in locomotor activity in ZD rats suggesting that the mechanisms responsible for increased physical activity in food restricted animals may be Zn dependent. Furthermore, differences in activity between PF and ZD animals were not reflected in differences in MR. Both ZD and PF significantly reduced MR compared with ZA rats beginning on day 4. There was a significant relationship between RQ and caloric intake (r = 0.708, P <.01), but no specific effect of Zn status. Thus, while there may be an effect of Zn on locomotion and the energetic cost of activity, it appears that the most profound effect of Zn status on MR and substrate utilization is the result of Zn deficiency-induced anorexia.