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Differential alterations in behavioural phenotypes, brain biochemical profiles and histomorphology in mice after prolonged administration of sildenafildapoxetine formulation

A. Omogbiya, O. Orovwigho, E. G. Moke, M. Oboh, J. O. T. Emudainohwo, P. E. Awhin, G. U. Saviour

African Journal of Tropical Medicine and Biomedical Research, 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 shortacting 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…

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