Abstract <p>D-serine is a ligand of the NMDA receptor glycine modulatorysite, and its exogenous administration can exert anxiolytic andpro-cognitive effects. PM (from “pendulum-like movements”) ratshave been selected for the presence of stereotypical hyperkinesisin the form of body and head swinging side to side. Additionally,they are characterized by an increased predisposition to audiogenicepilepsy, reduced learning abilities, and alterations in the brainglutamatergic system. The objective of this work was to study theeffects of low-dose D-serine on the characteristics of audiogenicseizures, behavior in the open field, light–dark box and elevated plusmaze tests, as well as spatial learning in the Barnes maze. It wasshown that D-serine at doses of 50 and 100 mg/kg has no effect onlocomotor activity in the open field and elevated plus maze tests.In the light-dark box test, an increase in the proportion of animalsdisplaying a D-serine-induced freezing response was found. In theBarnes maze test, the administration of 50 mg/kg D-serine did notinfluence either the time to find the escape box or the choice ofsearch strategy. The most significant outcome is the fact that D-serineat a dose of 100 mg/kg reduces the predisposition of PM rats toaudiogenic epilepsy, which requires further investigation.</p>