Copper chloride dose-dependently alters spatial learning and memory, and glutamate levels, in the hippocampus of rats

Copper is a trace element which exerts an important role in neuronal functions. Excessive Cu exposure is associated with central nervous system dysfunction, including memory loss. The present study examined the effects of CuCl2 exposure on the spatial learning and memory of rats, and on metabolites in the hippocampus. A total of 60 male Sprague‑Dawley rats (10 rats/group) were intraperitoneally injected with various doses (0, 0.5, 1.0, 2.0, 4.0 and 6.0 mg/kg) of CuCl2 three times every other day for 6 days. Rats administered with 1.0 ml/kg sterile saline were used as controls. A total of 2 days subsequent to the final injection, the rats were subjected to the Morris water maze (MWM) test, followed by proton magnetic resonance spectroscopy (1H‑MRS). The rats were subsequently sacrificed, and their hippocampal tissues were processed for high performance liquid chromatography (HPLC). The MWM test demonstrated that the high‑dose groups exhibited worse spatial learning and memory compared with the controls; however, the rats that received a relatively low dose (2.0 mg/kg) exhibited a decreased impairment. The 1H‑MRS results revealed increased Glu, N‑acetyl‑L‑aspartate (NAA)+N‑acetylaspartylglutamate, phosphocreatine (PCr) and Cr+PCr levels in the hippocampus of the 2.0 mg/kg group. HPLC analysis revealed increased γ‑aminobutyric acid and glutamate (Glu) levels in the 2.0 mg/kg group, and decreased Glu levels in the 6.0 mg/kg group. The results of the present study demonstrated a beneficial effect of short‑term exposure to a relatively low dose of CuCl2 on spatial learning and memory, and the association of this effect with increased NAA and Glu levels in the hippocampus.