Vinpocetine Improves Scopolamine Induced Learning and Memory Dysfunction in C57 BL/6J Mice

Abstract

Vinpocetine is an inhibitor of phosphodiesterase type 1 (PDE1), which has been used for treating stroke for over 40 years. However, according to current clinical dosage and treatment period, its direct effect on memory is unclear. In this study, we investigated whether vinpocetine could reverse the scopolamine (SCO)-induced cognitive deficits in animals. Behavioral experiments, including open field, Y-maze, and fear conditioning tests were used to determine the possible role of vinpocetine on scopolamine-induced memory dysfunction. In the open field and Y-maze tests, there were significant differences between the control (CON) group and SCO group. Vinpocetine (4 mg/kg) administration for consecutive 28 d significantly improved the scopolamine-induced memory dysfunction. In the fear conditioning test, vinpocetine (2, 4 mg/kg) administration had certain beneficial effect on emotional memory. Our results suggest that vinpocetine could improve cognitive function in memory deficient mice and high clinic dosage might be better. Key words vinpocetine; scopolamine; memory dysfunction; behavior testDiscovered in the late 1960 s, 1) it is currently popular in China and Hungary for treating cerebral ischemia. Its structure is shown in Fig. 1.2) Although used in the treatment of cerebral ischemia for over 40 years, vinpocetine is widely marketed only as a dietary supplement for vasodilation and as a nootropic for the improvement of memory 3); it has not been approved by any regulatory body for the treatment of cognitive impairment.2,4,5) Many basic science studies have shown that vinpocetine has a variety of potentially important effects on the brain. Despite these proposed mechanisms and targets, the relevance of these basic science findings in clinical studies is unclear. As an inhibitor of phosphodiesterase type 1 (PDE1), it increases cAMP and cGMP levels to increase blood circulation and metabolism in the brain. 6,7)Vinpocetine might enhance memory deficit through the modulation of cholinergic functions. 8) Traditionally, scopolamine (SCO) has been used in the field of neuropsychopharmacology as a standard/reference drug for dementia-related cognitive deficits model. 9) Deshmukh et al. found chronic treatment with vinpocetine (5, 10 and 20 mg/kg intraperitoneally (i.p.)) for 21 d following first intracerebro-ventriculas (i.c.v.) streptozotocin infusion significantly improved learning and memory in Morris water maze and passive avoidance paradigms.10) DeNoble et al. found that vinpocetine (3 mg/kg per os (p.o.)) was also effective in preventing disruption of passive avoidance retention impaired by 7% oxygen-induced hypoxia.8) These data support the view that vinpocetine can improve cognitive ability on scopolamine and hypoxia-induced memory impairment rats, but whether it could improve memory effects by clinical dosage and treatment period is still unclear.In the present study, we used behavioral analyses to test the possible role of vinpocetine on scopolamine-induced dementia in C57BL/6J mice by clinical dosage and trea...

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“…84,85 Indeed, the natural β-carboline vinpocetine inhibits PDE1 and shows beneficial effects on memory function in rats. 86 To the best of our knowledge, vinpocetine is the only β-carboline described to inhibit PDE1, a dual substrate enzyme able to hydrolyze both cAMP and cGMP. There are few studies of β-carboline on PDE targets other than PDE5.…”

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“…This has been demonstrated by the effect of vinpocetine in improving chronic hypoperfusion [37,38]. Increased cerebral metabolism might be induced through enhanced cerebral flow, increased oxygen and glucose consumption in the brain and increased ATP production [36].…”

“…It has been shown to improve cognitive function and short term memory in both animals and humans and has also been found to be useful in cerebrovascular disease. It is remarkably safe and also possesses antioxidant activity against free radicals and toxic substances [35,36]. Vinpocetine acts by increasing blood circulation and cerebral metabolism in the brain.…”

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