Background: Animal models of copper toxicities rarely exhibit neurological impairments and increased brain copper accumulation impeding the development of novel therapeutic approaches to treat neurodegenerative diseases having high brain Cu content. Aims: The aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g b.w.) daily for 90 days on copper and zinc levels in liver, kidney and hippocampus; expression of hepatic metallothionein-I and Atp7b gene, with metallothionein-III and acetylcholine esterase (AChE) gene in brain, biochemical parameters and neurobehavioral functions (by Morris water maze) of male wistar rats. Results: Copper administered animals exhibited significantly decreased serum AChE activity, increased hepatic metallothionein-I gene expression, impaired neuromuscular coordination and spatial memory compared to control rats. Copper intoxicated rats showed significant increase in liver, hippocampus and kidney tissues copper content (99.1, 73 and 74.9 % increase respectively), 40.7 % reduction in hepatic zinc content and interestingly, 77.1% increase in hippocampus zinc content with concomitant increase in copper and zinc levels in serum and urine compared to control rats. Massive copper deposition and copper associated protein in hepatocytes of copper intoxicated rats was substantiated by rhodanine and orcein stains respectively. Copper intoxicated rats demonstrated swelling and increase in number of astrocytes, degenerated neurons having pyknotic nuclei with copper deposition in choroid plexus. Conclusion: Present study shows the first evidence in vivo that chronic copper toxicity causes impaired spatial memory, swelling of astrocytes, decreased serum AChE activity,