Paracetamol--the outcome on neurotransmission and spatial learning in rats.

The present study was aimed at investigating the effect of subcutaneous (s.c.) paracetamol administration on spatial learning, memory and neurotransmission. Three-month old male Wistar rats received for eight weeks paracetamol at two doses: 10mg/kg b.w. (group P10, n=9) or 50mg/kg b.w. per day s.c. (group P50, n=9). Control (Con, n=9) and paracetamol-treated groups have been observed for behavioral performance and learning in the modified Morris water maze task. After completion of the behavioral data, the regional brain concentrations of neurotransmitters and their metabolites were determined using High Performance Liquid Chromatography (HPLC) in the prefrontal cortex, hippocampus, hypothalamus and the striatum. ANOVA for repeated measurements did not show significant differences between the groups in the acquisition in the water maze test. However, working memory improvement was noticed in P10 and P50 during second day of training. Results of the probe trial on day 6 indicated an increase in the mean swimming speed following subcutaneous drug treatment. Significant differences in the content of monoamines and metabolites between the experimental groups suggests that major changes after paracetamol administration are related to serotonergic and noradrenaline neurotransmission in the prefrontal cortex, hypothalamus and the striatum. The present experiment demonstrates that eight-week long subcutaneous paracetamol treatment results in significant modulation of neurotransmission with subtle changes concerning behavior and working memory in rats.