The protective and therapeutic effects of vinpocetine, a PDE1 inhibitor, on oxidative stress and learning and memory impairment induced by an intracerebroventricular (ICV) injection of amyloid beta (aß) peptide.

ABSTRACT

Alzheimer's disease (AD) is a neurodegenerative disease leading to cognitive and memory impairment. This study aimed at investigating the therapeutic and preserving effects of vinpocetine on amyloid beta (Aß)-induced rat model of AD. Sixty male adult Wistar rats were randomly divided into 6 groups (n = 10 per group) as follows 1; control, 2; sham, 3; Aß, 4; pre-treatment (vinpocetine + Aß) oral gavage administration of vinpocetine at 4 mg/kg for 30 days followed by intracerebroventricular (ICV) injection of Aß, 5; treatment (Aß + vinpocetine) Aß ICV injection followed by vinpocetine administration for 30 days, 6; pre-treatment + treatment (vinpocetine + Aß + vinpocetine) vinpocetine administration for 30 days before and 30 days after AD induction. Following treatments, the animals' learning and memory were investigated using passive avoidance learning (PAL) task, Morris water maze (MWM), and novel object recognition (NOR) tests. The results demonstrated that Aß significantly enhanced escape latency and the distance traveled in the MWM, decreased step-through latency, and increased time spent in the dark compartment in PAL. Vinpocetine ameliorated the Aß-infused memory deficits in both MWM and PAL tests. Administration of vinpocetine in the Aß rats increased the discrimination index of the NOR test. It also significantly diminished the nitric oxide and malondialdehyde levels and restored the reduced glutathione (GSH) levels. Vinpocetine can improve memory and learning impairment following Aß infusion due to its different properties, including antioxidant effects, which indicates that vinpocetine administration can lead to the amelioration of cognitive dysfunction in AD.