Ammonia-induced deficit in corticostriatal long-term depression and its amelioration by zaprinast.

Hyperammonemia is a major pathophysiological factor in encephalopathies associated with acute and chronic liver failure. On mouse brain slice preparations, we analyzed the effects of ammonia on the characteristics of corticostriatal long-term depression (LTD) induced by electrical stimulation of cortical input or pharmacological activation of metabotropic glutamate receptors. Long exposure of neostriatal slices to ammonium chloride impaired the induction and/or expression of all studied forms of LTD. This impairment was reversed by the phosphodiesterase inhibitor zaprinast implying lowered cGMP signaling in LTD suppression. Polyphenols from green tea rescued short-term corticostriatal plasticity, but failed to prevent the ammonia-induced deficit of LTD. Zaprinast counteracts the ammonia-induced impairment of long-term corticostriatal plasticity and may thus improve fine motor skills and procedural learning in hepatic encephalopathy.