Behavioural and molecular study of the effects of rosuvastatin on acquisition and retention of spatial memory impaired by H-89 in rats

There is controversy on the effect of statins on cognitive functions such as spatial memory. In the present study, effect of ten- day oral gavage of rosuvastatin (Ros, 20 mg/kg) on spatial learning and spatial memory retention impaired by H-89, was investigated in male rats. This study was comprised of two sets of experiments each including the following 3 groups (n = 8): Control group treated with DMSO; H-89 group received bilateral intra-hippocampal H-89 (10 μM/side, in DMSO) and Ros- H-89 group orally treated with Ros (20 mg/kg) and H-89 (similar to the H-89 group). For spatial learning (acquisition phase) assessment, from day 7 of Ros gavage, rats were trained in the Morris water maze (MWM) for four days (one block of 4 stages each day) and received daily H-89, 30 min after Ros gavage. On day 11, the probe test was performed. Also, to assess spatial memory retention, from day 7 to 10 of Ros gavage, rats were trained in MWM but received H-89 on day 10 only. On day 12, the probe test was performed. Besides, CREB and p-CREB protein expression was assessed in hippocampal samples and oxidative stress status was assessed in serum samples. We observed that H-89 led to a clear impairment of the spatial learning and spatial memory recall, increased levels of lipid peroxidation and downregulated CREB and p-CREB proteins, compared to the control group. However, Ros prevented H-89-induced deleterious consequences which might be probably in part due to its ameliorative effects on lipid peroxidation index and CREB and p-CREB expression