Effect of xanthine derivatives on hippocampal long-term potentiation

The effect of the structurally similar xanthine derivatives, propentofylline, pentoxifylline and theophylline, on long-term potentiation (LTP) recorded in CA3 of hippocampal slices of guinea pigs was investigated. A concentration-dependent increase in the amplitude of the population spike of CA3 pyramidal neurons was evoked by bath application of propentofylline and theophylline with a threshold concentration of 10 microM. This increase returned to the control level after washout for 20-30 min. Propentofylline enhanced LTP with a threshold concentration of approximately 5 microM. Pentoxifylline and theophylline enhanced LTP with threshold concentrations between 100 and 1000 microM. The enhancement of LTP lasted for more than 30 min after washout of the xanthines. The effect of propentofylline (10 microM) on LTP was blocked either by the beta-adrenoceptor antagonist propranolol (1 microM) or theophylline (10 microM). These results suggest that (i) the mode of action of propentofylline in enhancing LTP differs from that of pentoxifylline and theophylline and (ii) norepinephrine and adenosine are involved in the effect of propentofylline on LTP.