N-(p-amylcinnamoyl) anthranilic acid attenuates remedial effects of memantine on memory deficits following intracerebroventricular streptozotocin administration in rats.

N-(p-amylcinnamoyl) anthranilic acid (ACA) is a blocker of transient receptor potential melastatin-2 (TRPM2) which is a non-selective, Ca2+-permeable and oxidative stress sensor cation channel. Intracerebroventricular (ICV) streptozotocin (STZ) induction successfully generates spatial memory deficits in rats. The purpose of this study was to investigate effects of ACA on a rat model of STZ-induced learning and memory deficits. A total of 60 Wistar rats randomly divided into six groups; (1) control, (2) sham-operated, (3) ICV-STZ administered, (4) ICV-STZ + memantine (5 mg/kg i.p.), (5) ICV-STZ + ACA (25 mg/kg i.p.) and (6) a combination therapy group, ICV-STZ + ACA (25 mg/kg) + memantine (5 mg/kg). Effects of the drugs on spatial memory deficits were appraised in Morris water maze (MWM) apparatus. Anxiety-like behavior of the rats were also assessed by using both the elevated plus maze (EPM) and open field maze (OFM) apparatuses. Western blot analysis of hippocampal tissues revealed TRPM2-L channel protein expression levels. Serum levels of tumor necrosis factor alpha (TNF-α) and malondialdehyde (MDA) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Memantine treatment ameliorated the spatial memory deficits induced, as evidenced by the MWM tests. However, ACA treatment did not provide any improvement, instead positive effects of memantine were attenuated by ACA treatment. Western blot analysis in hippocampal tissues showed that TRPM2-L protein expression was markedly suppressed in ICV-STZ administered group. The ACA treatment reversed that suppression. Surprisingly, the memantine treatment resulted in overexpression of TRPM2-L, to a certain extent. Examination of the rats in EPM and OFM apparatuses, as a display of anxiety-like behavior, did not reveal any marked difference among groups. Serum levels of TNF-α and MDA also did not vary significantly among groups, as well. Conclusively, our findings showed for the first time that TRPM2-L protein expression was significantly suppressed in the ICV-STZ induced memory deficit model. Even though ACA reversed this suppression, no improvement in spatial memory was observed following ACA treatment.