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RESEARCH JOURNAL OF PHARMACY AND TECHNOLOGY
Year : 2020, Volume : 13, Issue : 12
First page : ( 6041) Last page : ( 6049)
Print ISSN : 0974-3618. Online ISSN : 0974-360X.
Article DOI : 10.5958/0974-360X.2020.01053.7

Testosterone undecanoate effects on behavior and cognitive functions in male swiss albino mice exposed to chronic social defeat

Ibrahim M.K.1, Tikamdas R.24, Kamal M.23, Nouh R.A.4, Sayed M.24

1Department of Developmental Pharmacology, National Organization for Drug Control and Research (NODCAR), Giza, Cairo.

2Center of Drug Research and Development (CDRD), College of Pharmacy, The British University in Egypt (BUE), El-Sherouk City, Egypt.

3Department of Biochemistry, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Egypt.

4Department of Clinical Pharmacy Practice, Faculty of Pharmacy, The British University in Egypt, El-Sherouk City, Egypt.

*Corresponding Author E-mail: helmy.mostafa@bue.edu.eg

Online published on 15 February, 2021.

Abstract

Objective: To examine the impact of exogenous testosterone undecanoate (TU) on chronic stress-induced behavioral changes of sensory contact model in adolescent male Swiss Albino mice. Design: Stress was induced by sensory contact model (SCM) for 12 consecutive days. Defeated mice were randomly assigned to control group (vehicle), testosterone undecanoate (100mg/Kg) (TU 100) or testosterone undecanoate (500mg/Kg) (TU 500) given intramuscular once for 45 days administered 2 hours after the last SCM session. Results: SCM significantly reduced distance traveled, time spent in the center, average speed in the open field test compared to negative control group. In addition, SCM significantly reduced preference index of defeated group in the NOR test, time spent in the open arms in the EPM test, reduced escape time and time in the quadrant in Morris water maze test (MWM) when compared to the negative control group.SCM significantly reduced the mRNA expression of CREB in the hippocampus of defeated group when compared to the negative control group. In the open field test, TU 500 treatment showed a significant increase in both distance traveled and average speed compared to the defeated group, while TU 100 treatment did have an anxiolytic effect indicated by the significantly increased time spent in the center and the significantly reduced time spent in the corner and the significantly reduced immobility time when compared to the defeated group. Both TU 100 and TU 500 did improve the retention memory indicated by the significant increase in the preference index compared to the defeated group in the NOR test. In the EPM test, both TU 100 and TU 500 did show an anxiolytic effect through a significant increase in the time spent in the open arms and a significant reduction in the time spent in the closed arms compared to the defeated group. In MWM, both TU 100 and TU 500 showed a significant improvement in learning memory as indicated by a significant reduction in the escape time and a significant increase in the time spent in the target quadrant on the probe day. Interestingly, TU 500 treatment showed a significant increase in CREB relative mRNA expression in the prefrontal cortex region compared to both defeated and negative control groups. Conclusion: Exogenous testosterone administration ameliorated some age-related neurobehavioral responses after exposure to chronic social defeat; however, more studies are needed to clarify the mechanisms that underlie them.

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Keywords

Sensory contact model, Testosterone undecanoate, CREB, Chronic stress.

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