The role of galanin on long-term potentiation (LTP) of the field excitatory postsynaptic potentials (fEPSPs)at Schaffer collateral-CA1 synapses was investigated in guinea-pig hippocampal slices. Application of galanin (10(-7) M) inhibited the magnitude of LTP without any changes in the amplitude of fEPSP prior to tetanic stimulation. A putative central nervous system (CNS) type galanin receptor antagonist, galanin(1-13)-Pro-Pro-(Ala-Leu)(2)-Ala-Amide (M40), did not modify the magnitude of LTP when applied alone. However, M40 significantly reversed the inhibition by galanin when applied with galanin simultaneously. These findings suggest that galanin plays an inhibitory role through the CNS type galanin receptors.