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 μM) 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.