Depression is a mental illness with a high prevalence in humans reaching 21% of the worldwide population.The present study aims to evaluate the antidepressant effect of different formulations of Thymoquinone; free Thymoquinone (TQ), Thymoquinone-loaded Chitosan nanoparticles (TQ-TPP-Cs NPs) and Thymoquinone-loaded Chitosan nanoparticles coated with polysorbate 80 (TQ-TPP-Cs NPs-PSb80) that have been prepared to avoid the low bioavailability of TQ. Rats were randomly separated into control rats, depression control induced by reserpine, rat model treated with TQ, rat model treated with TQ-TPP-Cs NPs and rat model treated with TQ-TPP-Cs NPs-PSb80. The results indicate that TQ-TPP-Cs NPs loaded with polysorbate 80 was more efficient in ameliorating the behavioral and neurochemical changes induced by reserpine than TQ and TQ-TPP-Cs NPs. Formulationswere characterized for size, morphology, encapsulation efficiency and in vitro drug release before their use in treatment. Reserpine induced a reduction in motor activity and swimming time and increased immobility time as indicated from the open field test (OFT) and forced swimming test (FST). In addition, a significant decrease in the monoamine neurotransmitters serotonin (5-HT), norepinephrine (NE) and dopamine (DA) was recorded in the cortex, hippocampus and striatum of reserpine-treated rats. The present data suggest that the antidepressant efficacy of TQ could be enhanced by engaging TQ with chitosan nanoparticles as a drug carrier and the formulations were modified by coating with polysorbate 80.
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