Abstract <p>In this study, the effects of sodium metabisulfite (Na₂S₂O₅) on learning and memory as well as the relationship of these effects with arachidonic acid, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) signal pathway and PGE2 receptor subtypes were investigated. 3-months-old male Wistar rats were divided into 3 groups as control (C), S100 and S260. The C group were given tap water for 35 days via gastric gavage, while S100 and S260 groups were received sodium metabisulfite at doses of 100 mg/kg (S100) and 260 mg/kg (S260) for the same period. Morris water maze (MWM) and open field (OF) test were performed. After behavioral tests, blood samples were collected and their brain tissues were removed. In the hippocampus, arachidonic acid (AA), PGE2 levels and COX-2 activity were determined and mRNA levels of PGE2 receptor subtypes were analyzed with RT-PCR. In Na₂S₂O₅ groups, the total distance and average velocity values in the MWM tests increased, while target quadrant entrance frequency decrease. Total distance and average velocity in the OF test, plasma S-sulfonate and AA levels in Na₂S₂O₅ groups were significantly higher compared to control group. PGE2 level and COX-2 activity were found to be significantly higher only in S260 group. However, mRNA expressions of PGE2 receptor subtypes in the hippocampus increased significantly in the S100 group. In our study, Na₂S₂O₅ intake above the safe dose impaired learning and spatial memory, and this deterioration may involve neurobiological mechanisms mediated through the AA, COX-2, PGE2 pathway and PGE2 receptor subtypes.</p>