ANTAGONISTS OF THE PLATELET-ACTIVATING-FACTOR RECEPTOR BLOCK LONG-TERM POTENTIATION IN HIPPOCAMPAL SLICES

The effects of antagonists and agonists of the platelet-activating factor (PAF) receptor on the formation of long-term potentiation (LTP) were examined in slices of rat hippocampus. The antagonist trans-BTD 1(trans-2,5-bis-(3,4,5-trimethoxyphenyl)-1,3-dioxolane) at concentrations of 8-16-mu-M blocked LTP in field CA1 while the same concentration of a stereo isomer (cis-BTD) with low affinity for PAF receptors was without effect. CV3988, an antagonist structurally related to PAF, also attenuated LTP. The blockade of LTP by trans-BTD was partially reversed by simultaneous application of the non-metabolizable receptor agonist carbamyl-PAF. Trans-BTD did not change the following physiological measures: (i) paired-pulse facilitation, (ii) responses occurring during the short bursts given to induce LTP, (iii) N-methyl-D-aspartate receptor-mediated responses, and (iv) potentiation measured during the first minute after high-frequency stimulation. It thus appears that trans-BTD interferes with LTP at some step after induction and initial expression. These results suggest that activation of PAF receptors contributes to the stabilization of LTP, possibly via an effect on intracellular calcium levels.