MWM test employed in the present study is one of the most widely accepted models to evaluate learning and memory of the animals.[7
] A significant decrease in day 4 ELT of control animals during the ongoing acquisition trials denoted normal acquisition of memory and an increase in TSTQ in search of missing platform during retrieval trial indicated retrieval of memory. These results are consistent with our earlier findings.[11
] In the present study, scopolamine produced impairment of acquisition and retrieval of memory, as reflected by significant increase in day 4 ELT and decrease in day 5 TSTQ, respectively. Acetylcholine (ACh) is a classic mediator of learning and memory. Drugs that reduce cholinergic function, such as muscarinic receptor antagonist scopolamine, cause profound memory impairments in animals and humans.[12
] The degeneration and dysfunction of cortical cholinergic neurons is closely associated with cognitive deficits of AD.[13
] These findings provide a cholinomimetic rationale for the treatment of dementia closely related to AD and support the use of animal models using muscarinic receptor antagonists.[6
] This contention is further supported by our study, whereby a significant impairment of learning and memory in rats treated with scopolamine has been observed. Moreover, scopolamine treatment also produced a significant enhancement of brain AChE activity and increase in oxidative stress, as indicated by a rise in brain TBARS and reduction in GSH levels, which is in line with previous findings.[14
In the present investigation, pretreatment of stevioside abolished scopolamine-induced memory deficits along with attenuation of scopolamine-associated increase in brain oxidative stress levels and brain AChE activity. Stevioside, being the main sweet component in the leaves of Stevia rebaudiana Bertoni
, has recently gained much attention as a sweetener.[15
] It has no caloric value and thus could be used to reduce sugar intake in diabetics, obese and patients of phenylketonuria.[16
] Stevioside, in addition to its sweetening property, has also been reported to exert many other effects, including antioxidative and antiinflammatory actions.[5
Studies in the recent past have documented the important role of sweetening agent, i.e. glucose, in learning and memory, and there is extensive evidence in the literature indicating that modest increase in circulating glucose levels enhances the formation of new memories in rodents and humans.[17
] Glucose administration has been reported to enhance the memory processes by increasing hippocampal ACh synthesis and release.[18
] Furthermore, extracellular brain glucose levels have been demonstrated to vary with neuronal activity, suggesting that circulating glucose may be critical in modulating neural processes important for memory functioning.[19
Therefore, from the above findings, it is evident that stevioside abolished scopolamine-induced memory deficits. This effect may be attributed to its sweetening property. However, its potential antioxidative and antiinflammatory actions also cannot be ignored because brain oxidative stress and inflammation play a critical role in the pathobiology of dementia. Moreover, the observed anticholinesterase action of stevioside in the present investigations might also have played an important part in its antiamnestic action.
Therefore, it may be concluded that stevioside exerts its beneficial effect in scopolamine-induced memory deficits by virtue of its sweetening, antioxidative, antiinflammatory and anticholinesterase actions. Nevertheless, further studies are needed to explore the full potential of stevioside in memory deficits.