Effects of zinc on spatial reference memory and brain dopamine (D1) receptor binding kinetics in rats

1. The present study was designed to evaluate the effects of zinc on spatial reference memory and brain dopamine (D1) receptor binding kinetics in rats. Male Sprague-Dawley rats (120-150 g), adapted 12 hour light: 12 hour dark illumination cycle were used. Treated animals were given zinc chloride (25 mg/kg, 50 mg/kg, or 100 mg/kg) by oral gavage for 15 days at 11:00 hr. Controlrats received an equivalent volume of saline. 2. Spatial reference memory was evaluated in treated and control rats on days 10 through 15 using the Morris Water Maze. The time to find the platform (latency) was significantly increased in the 50 mg/kg and 100-mg/kg zinc treated animals as compared to the controls. One hour after the last spatial reference memory testing, the animals were sacrificed by decapitation; their brains were removed and dissected into various regions. 3. D1 receptor binding kinetics were measured using the ligand [3H] SCH23390. Results obtained indicate that zinc chloride administration resulted in a statistically significant decline in the binding affinity (increased Kd) of the D1 receptors in the frontal cortex, hypothalamus, hippocampus, and midbrain. However, there was a significant increase in the D1 receptor binding capacity (Bmax) in these same brain regions following zinc chloride administration. 4. These findings clearly indicate that administration of high doses of zinc to rats resulted in spatial reference memory deficit, which may in part be explained by alterations in dopamine receptor binding kinetics.