ORIGINAL ARTICLES

Differential Alterations In Behavioural Phenotypes, Brain Biochemical Profiles And Histomorphology In Mice After Administration Of Sildenafil-dapoxetine Formulation

Orovwigho Ogheneoruese
Omogbiya Adrian Itivere
Moke Emuesiri Goodies
Maxwell Oboh
Emudainohwo J.O. Tedwins
Awhin Ejiro Prosper
Usin Saviour God's wealth
Published: December 1, 2025

Abstract

Introduction: Cognition encompasses the brain's processes for learning, memory and decision making - functions highly dependent on balanced neurotransmission and oxidative stability. In recent years, aphrodisiac misuse - particularly sildenafil, a phosphodiesterase-5 inhibitor, and dapoxetine, a short-acting selective serotonin reuptake inhibitor - has become prevalent among young adults seeking sexual enhancement without medical supervision. However, the neurocognitive implications of their prolonged use are poorly understood. Hence, this study investigated the cognitive and biochemical effects of prolonged sildenafil-dapoxetine (SIL-DAP) exposure in experimental mice.

Materials and Methods: Adult male mice were divided into seven groups and orally given distilled water, VEH (10 mL/kg), scopolamine (1 mg/kg), sildenafil (1 mg/kg), dapoxetine (1 mg/kg), SIL-DAP (2.5 mg/kg and 5.0 mg/kg), or donepezil (1 mg/kg), respectively, for 60 days (at 2-day intervals). Twenty-four hours after the last treatment, behavioural paradigms (Barnes maze and Rota rod tests) were assessed, followed by biochemical assays of oxidative stress indices (SOD and MDA) and histopathological evaluations in the brain - the prefrontal cortex and hippocampus.

Results: Results show that 30-day SIL-DAP administration enhanced spatial memory, evident as increased escape latency in the Barnes maze, increased coordination in the Rota rod test and enhanced antioxidant enzyme activity. However, prolonged exposure produced dose-dependent neuronal degeneration and reduced antioxidant defence. Histological alterations revealed necrosis within the prefrontal and hippocampal regions, indicating oxidative neurotoxicity.

Conclusion: Collective findings suggest that while acute SIL-DAP use may transiently improve cognition, chronic misuse disrupts redox balance and neuronal integrity, predisposing users to cognitive decline.

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Published in Vol. 8 No. 2 (2025): African Journal of Tropical Medicine and Biomedical Research, December 2025.

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Orovwigho O, Itivere OA, Moke EG, Oboh M, Emudainohwo JT, Awhin EP, et al. Differential Alterations In Behavioural Phenotypes, Brain Biochemical Profiles And Histomorphology In Mice After Administration Of Sildenafil-dapoxetine Formulation. Afr. J. Trop. Med. Biomed. Res. [Internet]. 2025 Dec. 1 [cited 2026 May 31];8(2):12-26. Available from: https://www.ajtmbr.org.ng/index.php/home/article/view/185

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