Effect of Chromium Picolinate on Modified Forced Swimming Test in Diabetic Rats: Involvement of Serotonergic Pathways and Potassium Channels

Abstract

Depression occurs frequently in patients with diabetes mellitus. Chromium picolinate, an essential trace element is recommended for diabetes and also has been reported to benefit depression, but its mechanism is still debated. To investigate the mechanism, we studied its effects on serum insulin, serum glucose and on modified forced swimming test, a behavioural paradigm for depression in rats. The study involving co-administration of subactive doses of glimepiride, a K π channel blocker and chromium picolinate on blood glucose levels and modified forced swimming test was also performed to probe any role of K π channels in its antidiabetic and antidepressants effects. Streptozotocin (55 mg/kg, intraperitoneally) was injected in rats to induce diabetes (Type 1). After a week, chromium picolinate (8 mg/ml in drinking water) was administered for 4 weeks. Normal rats received similar drug treatment. The subactive doses of chromium picolinate (4 mg/ml in drinking water) and glimeperide (2.5 mg/kg, orally) were co-administered and their effects on modified forced swimming test and on glucose levels were measured. Chromium picolinate (8 mg/ml in drinking water) produced hypoglycaemia in diabetic and normal rats. It had no effects on the streptozotocin-induced reduction in insulin levels. Chromium picolinate (8 mg/ml in drinking water) increased swimming with subsequent decrease in immobility. The subactive doses of chromium picolinate and glimeperide showed significant additive effects in modified forced swimming test and reduction in serum glucose concentrations, though statistically insignificant. In conclusion chromium picolinate shows antidepressant action on modified forced swimming test affecting only swimming that suggests serotonergic pathways involvement. The additive effects on swimming in modified forced swimming test and reduction in serum glucose levels shows involvement of K π channels in antidiabetic and antidepressant actions of chromium picolinate.The World Health Organization estimates that at least 170 million individuals globally suffer from diabetes (Elizabeth et al. 2004). Diabetes-related complications are major causes of morbidity and mortality. Many patients with diabetes eventually develop severe complications including amputations, blindness, kidney failure and cardiovascular disorders (Van Tilburg et al. 2001). Diabetes is also a significant risk factor for depression. Co-existing depression occurs in 10% to 30% of people with diabetes, and diabetic patients have 2 times increased risk of depression compared with people without diabetes (Leonard 2004). When depression accompanies diabetes, there is evidence of poor glycaemic control, decreased physical activity, obesity and potentially more diabetes end organ complications and impaired functions (Elizabeth et al. 2004). The hyperactivity of hypothalamic pituitary adrenal axis with hypercortisolaemia has been reported to be a physiological association in patients with diabetes and depression (Cameron et al. 1984). Over the past sever...

Effect of chromium on carbohydrate and lipid metabolism in a rat model of type 2 diabetes mellitus: the fat-fed, streptozotocin-treated rat

“…The translocation of glucose transporter 4 is mediated through insulin-independent phosphorylation and activation of AMPK [9]. In addition, recent studies [10,11] reported chromium action was absent in methyl-β-cyclodextrin-pretreated cells already displaying reduced plasma membrane cholesterol and increased glucose transporter 4 translocation, and these findings at the cell level are consistent with in vivo observations of improved glucose tolerance and decreased circulating cholesterol levels after chromium supplementation and serotonergic pathway involvement [12]. Early reports suggested that chromium enhances insulin binding, insulin receptor number, insulin internalization, and beta-cell sensitivity [13].…”

The Effects of Chromium Complex and Level on Glucose Metabolism and Memory Acquisition in Rats Fed High-Fat Diet

“…In experiments involving animals, however, it is impossible to examine directly the level of depression, but some behavioral features can be attributed to central nervous system activity. Hippocampal-dependent learning such as acquisition of spatial memory, long-term memory, and long-term spatial memory can be evaluated by various tests [21,23,63]. Diabetes-induced rats overcame a behavioral paradigm upon forced swimming test as reflected by increased percentage preference to open arm in elevated plus maze spontaneous alternation behavior paradigm as a measure of anxiety and memory [64,65] due to anxiolytic action of Cr through noradrenergic and serotonergic pathway [66].…”

Effects of Pre- and Postnatal Exposure to Chromium Picolinate or Picolinic Acid on Neurological Development in CD-1 Mice

“…Significant increases in tryptophan, 5-HT, melatonin, and noradrenaline were noted after sub-chronic dosing with chromium picolinate in a study by Franklin and Odontiadis [15]. Other studies have indicated that Cr(pic) 3 may be effective at alleviating symptoms of depression in individuals with metabolic disorders, presumably by enhancing insulin function, without the side effects typically associated with more traditional treatments, such as monoamine oxidase inhibitors [13,[16][17][18][19]. However, the clinical studies with Cr(pic) 3 [16,17,19] utilized very limited subject pools and require larger trials to firmly establish whether the supplement can beneficially affect atypical depression.…”