Evaluation of molecular mechanism of modafinil on protein kinase aii inhibitor- induced spatial memory acquisition impairment in morris water maze in hippocampus of male rats by western-blot

Farzaneh Shamshirgaran,1 Kaveh tabrizian,2,* Mahmoud hashemzaei,,3 Najme nehi,4

1. Zabol University of Medical Sciences , Faculty of Pharmacy
2. Zabol University of Medical Sciences , Faculty of Pharmacy
3. Zabol University of Medical Sciences , Faculty of Pharmacy
4. Zabol University of Medical Sciences , Faculty of Pharmacy

Abstract


Introduction

Prescription of modafinil as a stimulant agent has been well documented in previous studies. the present research was designed to evaluate the effect of bilateral intra-hippocampal infusion of modafinil on h-89 (as a protein kinase aii inhibitor) –induced spatial learning alterations in the morris water maze (mwm) and also the evaluation of the expression of creb and pcreb proteins in the hippocampus of male rats.

Methods

In the present study, the effects of four-day bilateral intra-hippocampal infusion of modafinil (100, 250, 750 and 1000 μm/side) alone and in combination (100 μm/side) with h-89 (10 μm/side) on spatial learning was investigated in mwm in male rats. dmso was used as control for these groups. rats were trained for 4 days; each day included one block of four trials. post-training probe tests were performed on day 5 of study.

Results

H-89 -treated animals showed a significant increase in time and distance of finding the hidden platform and also a significant decrease in time spent in the target quadrant with a significant decrease in expression of creb and pcreb proteins compared to dmso -treated animals. the bilateral intra-hippocampal infusion of modafinil (100 μm/side) reversed h-89– induced spatial learning deficits with a significant increase in expression of creb and pcreb protein markers in comparison with h-89 –treated animals.

Conclusion

Taken together, the behavioral and molecular findings of this study indicated the possible regulatory effects of modafinil on the camp / pka / creb signaling pathways.

Keywords

Modafinil, protein kinase aii, spatial learning, creb, pcreb