Frontiers Journal of Neurology & Neuroscience

Effect Of Chronic Paracetamol Treatment On The Alteration Of Learning And Memory


In this study, the alterations in learning and memory behaviors and brain-derived neurotrophic factor (BDNF) expression following APAP treatment were investigated. Two doses of APAP (50 and 200 mg/kg bw) were orally fed to male Wistar rats through either a single treatment (0 days), sub-chronic treatment (15 days) or chronic treatment (30 days) regimen. Alterations of learning and memory were evaluated by novel object recognition (NOR) and Morris water maze (MWM) tests. Expression of BDNF protein was monitored in the frontal cortex and hippocampus using Western blot analysis. Acute APAP treatment (0-day treatment) at any dose had no effect on NOR performance. Treatment with low-dose APAP (50 mg/kg bw) for longer duration could enhance the learning and memory performance. In contrast, deficits in learning and memory were clearly observed in rats chronically treated with 200 mg/kg bw of APAP. There were no alterations in the frontal cortical and hippocampal BDNF expression in rats treated with APAP (50 and 200 mg/kg bw) for 0 and 15 days. With 30-day treatment, 50 mg/kg bw APAP could increase the BDNF expression in those brain areas while the significant decrease in BDNF protein was observed in rats with 200 mg/kg bw APAP treatment. Our results suggest that the bi-directional effects of long-term APAP treatment depend on the dose of the treatment. An alteration of the BDNF level in the frontal cortex and hippocampus due to the APAP treatment is possibly involved in the bi-directional effects of APAP on learning and memory.