The impairment of cognitive performance by galanin administration in rodents indicates a possible modulating effect of this neuropeptide on long-term potentiation (LTP) induction in the hippocampal formation. Galnon is a non-peptide, systemically active galanin receptor agonist which has been tested in feeding, seizure and forced swim task in in vivo rodent experimental models. Similarly to galanin (1-29) (i.c.v.), galnon (i.p.) has exhibited anticonvulsant effects in rats. We have investigated the effect of galnon on the synaptic transmission and plasticity in hippocampal dentate gyrus (DG) of C57Bl/6 mice and compared the galnon effects to the effect of galanin (1-29) and galmic, a non-peptide galanin receptor agonist. Similarly to galanin (1-29) and galmic, superfusion of galnon did not alter the input-output responses in DG. Administration of galnon (1 microM) significantly attenuated the LTP induction by 85.5 +/- 1% by 51 min after high frequency trains stimulation. This result was very similar to the effect of galanin (1-29) and galmic, which caused an 80 +/- 1.5% and 94 +/- 2% reduction in the level of field potentiation, respectively. The PPF responses, however, were not altered due to galnon superfusion which is in contrast to the effect of galanin (1-29) or galmic. In summary, these data indicate that the systemically active, non-peptide galanin receptor agonist, galnon can exert similar effects to galanin (1-29) in attenuation of DG LTP in mice.