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*
1Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran
4Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran
*corresponding author: karimian@tums.ac.ir
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Abstract:
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 intrahippocampal
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.

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