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BACKGROUND AND AIMS: The limbic glutamatergic neurotransmission may be involved in the biological mechanisms underlying anxiety-related disorders. The purpose of the present study was to determine the influence of NMDA glutamatergic receptor antagonist – D-AP7 infusions into the medial septum (MS) on time spent in open arms in rats differing in behavioral characteristics, stress susceptibility and anxiety level measured by their locomotor response to novelty: high (HRs) or low (LRs) responders under the elevated plus maze (EPM) test paradigm which is a rodent model of anxiety. METHODS: Male Wistar rats prior categorized as HRs or LRs in the novelty test (2 h) were exposed to the EPM test (5 min) in the baseline and 15 min after injection of D-AP7 (DL-2-amino-7- phosphoheptanoate, receptor antagonist; 0.1 µg/rat in 0.5 µl saline solution; n=15) or saline (0.5 µl/rat; n=12) via implanted cannulae into the MS. Data are presented as mean±SD. RESULTS: Following the D-AP7 injection, a significant increase in time spent in the open arms in both HRs (46±6 s) and LRs (102±6 s) within the D-AP7 group, in comparison with the baseline value (HR: 19±9 s, LR: 11±5 s; P≤0.001) and the SAL control group (HR: 24±9 s, LR: 19±9 s; P≤0.001), was observed. In the LRs, time in the open arms was significantly longer (LR: 102±6 s), as compared to the HRs (HR: 46±6 s; P≤0.001). CONCLUSIONS: The obtained results indicate that blocking of MS NMDA glutamate receptors decreases the expression of anxiety – like behavior, indicating by increased time spent in open arms in rats. This effect is more pronounced in rats with higher anxiety level but lower behavioral activity and stress susceptibility, which are attributed to the low responders. This study was supported by Gdańsk University grant for young scientists from Poland: 538-L124-B597-14.