Diphenylhydantoin facilitation of labile, protein-independent memory.

Diphenylhydantoin (DPH 10(-4)M) administered subcutaneously to chicks 5 min after a one-trial passive avoidance learning task successfully counteracted amnesia induced by pretreatment 5 min before learning with ouabain or cycloheximide (CXM). Biochemical assays confirmed that in chick forebrain homogenate DPH at concentrations of 1 and 5 X 10(-4)M enhanced Na+/K+ ATP'ase activity. Since both DPH and ouabain inhibit post-tetanic potentiation, the results support the hypothesis of an initial labile phase of memory based on sodium pump (Na+/K+ ATP'ase) activity. DPH was less effective in counteracting ouabain-induced amnesia if administered later than 10 min after learning and CXM-induced amnesia if administered later than 30 min after learning. This suggests that the effect of DPH on CXM-induced amnesia is through enhancement of Na+/K+ ATP'ase activity. It was suggested that the possible hyperpolarization of membrane potential associated with sodium pump activity may serve to mark the labile memory trace, enabling formation of a more permanent trace through protein synthesis.