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BEHAVIOURAL AND MOLECULAR STUDY OF THE EFFECTS OF ROSUVASTATIN ON ACQUISITION AND RETENTION OF SPATIAL MEMORY IMPAIRED BY H-89 IN RATS

KAVEH TABRIZIAN 1,2#, FATEMEH MIRI 3, SHIVA HASELI 3, JAFAR SHAHRAKI 1,2, MARYAM BELARAN 4, RAMIN REZAEE 5,6#, ALEKSANDRA BUHA 7, ARISTIDIS TSATSAKIS 8, ANDREEA LETIȚIA ARSENE 9, DRAGOȘ ȘERBAN 9, BRUNO ȘTEFAN VELESCU 9, MAHMOUD HASHEMZAEI 1,2*

1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
2 Toxicology and Addiction Research Centre, Zabol University of Medical Sciences, Zabol, Iran
3 Students Research Committee, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
4 Department of Physiology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
5 International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
7 “Akademik Danilo Soldatovic” Department of Toxicology, University of Belgrade-Faculty of Pharmacy, Belgrade, Serbia
8 Centre of Toxicology Science and Research, University of Crete, School of Medicine, Crete, Greece
9 “Carol Davila” University of Medicine and Pharmacy Bucharest, Romania

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There is controversy on the effect of statins on cognitive functions such as spatial memory. In the present study, effect of tenday 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 RosH-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.