Effect of oleuropein on morphine-induced hippocampus neurotoxicity and memory impairments in rats

Oleuropein, as an olive leaf extract antioxidant polyphenol, has been reported to be a free radical scavenger. This study was done to investigate the effects of oleuropein, against morphine-induced hippocampus neurotoxicity and memory impairment in rats. The Morris water maze (MWM) test was used to assess the effect of oleuropein (5, 15, and 30 mg/kg, i.p., co-administrated with morphine) on spatial learning and memory of male Wistar rats which were treated with morphine sulfate (45 mg/kg, s.c., 4 weeks). In order to evaluate the cleaved caspase-3, Bax, and Bcl2 protein expression (as biochemical markers of apoptosis) in CA1 area of hippocampus tissue, the western blot test was used. Also, to evaluate the oxidative stress status of hippocampus CA1 area tissue, the malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity were assessed. The data showed that oleuropein treatment (15 and 30 mg/kg) improves the spatial learning and memory impairments in morphine-treated animals. Also, oleuropein treatment decreased the apoptosis and oxidative stress levels in the hippocampus CA1 area of morphine-treated rats. Oleuropein can prevent the spatial learning and memory impairments in morphine-treated rats. Molecular mechanisms underlying the observed effects could be at least partially related to the inhibition of neuronal apoptosis and oxidative stress in the hippocampus CA1 area of morphine-treated rats.