Influence of the phosphodiesterase type 5 inhibitor,sildenafil,on antidepressant-like activity of magnesium in the forced swim test in mice

Magnesium,which acts as an antagonist of n-methyl-d-aspartate (nmda) subtype of glutamate receptors,exerts antidepressantlike activity in animal models of depression. the present study was undertaken to elucidate the influence of sildenafil,a phosphodiesterase type 5 inhibitor,on the anti-immobility action of magnesium in the forced swim test in mice. swim sessions were conducted by placing mice in glass cylinders filled with water for 6 min and the duration of the behavioral immobility during the last 4 min of the test was evaluated. locomotor activity was measured with photoresistor actimeters. serum and brain magnesium levels were assayed spectrophotometrically. magnesium at a dose of 30 mg/kg,ip significantly decreased the immobility time while sildenafil (5,10 and 20 mg/kg,ip) in a dose-dependent manner reduced the antidepressant-like activity of magnesium. the co-administration of magnesium with sildenafil at the highest dose entirely abolished the antidepressant-like effect of magnesium and caused a statistically significant increase in immobility duration as compared to the control group. combination of magnesium with sildenafil resulted in a potent reduction (80%) of locomotor activity and pharmacokinetic studies showed a significant increase of magnesium concentration in serum (as compared to magnesium treatment alone) without changes within brain tissue in mice treated with magnesium and sildenafil. when given alone,sildenafil caused a significant increase in magnesium levels in both serum and brain. our results indicate that a simultaneous treatment with magnesium and sildenafil results in hypermagnesemia in laboratory animals. however,the mechanism underlying this effect remains elusive. copyright © 2012 by institute of pharmacology polish academy of science.