Romanian Society of Pharmaceutical Sciences
 

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MODAFINIL PREVENTS TESTOSTERONE – PROVOKED SPATIAL LEARNING IMPAIRMENTS IN MORRIS WATER MAZE AND INCREASES THE QUANTITY OF BrdU-POSITIVE CELLS IN DENTATE GYRUS IN MALE RATS

MARYAM BELARAN1, MOHAMMAD SHARIFZADEH2, HAMID REZA SADEGHIPOUR1, KAVEH TABRIZIAN3, GHOLAMREZA HASANZADEH4, HAMIDREZA FAMITAFRESHI1, SEYED MORTEZA KARIMIAN1*

1.Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2 .Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3 .Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
4 .Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

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The relationships between the androgen receptors and cognitive processes in some brain regions such as hippocampus had been well documented in previous studies. The aim of this study was to evaluate the effect of bilateral intra-hippocampal infusion of modafinil on testosterone–induced spatial learning alterations in the Morris water maze (MWM) and also the evaluation of the quantity of BrdU-positive cells in dentate gyrus as a marker of cell proliferation. Bilateral intra-hippocampal infusions (1 µL/side) with different doses of testosterone enanthate (10, 50, and 100 µg/side) or modafinil (50, 100, and 250 µM/side) were performed, 30 min prior to training in MWM for four repeated days in male rats. Control groups received dimethyl sulfoxide (DMSO). The behavioural findings of this study, showed considerable raises in time and distance of reaching the hidden platform in testosterone (100 µg/side) – treated animals, and also significant decreases in above mentioned parameters in modafinil (100 µM/side) – treated group compared to their related control groups. We also assessed the effects of modafinil (50, 100, and 250 µM/side) plus testosterone enanthate (100 µg/side), on the spatial learning in MWM and the effect on neurogenesis by recording BrdU-positive in all above mentioned groups. Final results of this study showed that modafinil (100 µM/side) prevented the testosterone (100 µg/side) – induced spatial learning deficits in MWM and also increased the quantity of BrdU-positive cells in dentate gyrus in combination evaluations in comparison with testosterone – treated animals.