Affective Behavior Dysregulation Was Induced by Chronic Administration of Copper in Wistar Rats

Abstract

As both deficiency and excess of copper (Cu) can be harmful, dysregulation in its homeostasis has been connected with various neurological disorders. The present study was undertaken to examine whether Cu chronic administration can induce alterations of affective behavior especially anxiety and depression levels in male and female rats. Twenty-four rats, for each gender, divided in control and three test groups (n = 6), were injected intraperitoneally with saline (0.9% NaCl) or CuCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. Results demonstrated that Cu administered chronically, exerts an anxiogenic effect in rats. In the OFT, Cu decreases the TCA and NRC parameters without modifying the locomotor activity represented by the NTS parameter. With regard to EPM, Cu decreases TOA and EOA parameters without modifying the TAE parameter. A significant increase in depression-like symptoms was also exhibited by Cu treated rats (p < 0.001). A dose of 1 mg/kg CuCl2 showed maximum anxiety-like and depression-like symptoms as compared to controls as well as from the other two doses indicating dose-dependent effects of chronic Cu administration. Overall, these results suggest that intoxication with Cu has potentially deleterious effects on brain as reflected in behavioral dysfunctions such as depression and anxiety.