Romanian Society of Pharmaceutical Sciences

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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
2Toxicology and Addiction Research Centre, Zabol University of Medical Sciences, Zabol, Iran
3Students Research Committee, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
4Department of Physiology, Faculty of Medicine, Zabol University of Medical Sciences, Zabol, Iran
5International UNESCO Center for Health-Related Basic Sciences and Human Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
6Applied 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
8Centre 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.