Scopolamine-induced Memory Impairment In Rats Research Articles

Ameliorative effect of kolaviron, a biflavonoid complex from Garcinia kola seeds against scopolamine-induced memory impairment in rats: role of antioxidant defense system.

In Alzheimer's disease (AD) basal forebrain cholinergic neurons appear to be targeted primarily in early stages of the disease. Scopolamine (muscarinic receptor antagonist) has been used for decades to induce working and reference memory impairment in rodents. In this study, we evaluated the protective effect of kolaviron, a biflavonoid complex isolated from Garcinia kola seeds extract against scopolamine-induced memory impairment/oxidative stress. Rats were pretreated with kolaviron (25, 50 or 100mg/kg p.o.) for 3 consecutive days, scopolamine (3mg/kg, i.p.) was administered 1h post-treatment on day 3. Five minutes post-scopolamine injection, memory function was assessed using the Y-maze or Morris water maze tests (MWM) in rats. The rats were sacrificed and brains isolated on the 8th day after the MWM test for estimation of acetylcholinesterase activity and nitrosative/oxidative stress status. Scopolamine injection induced deficit (P<0.05) in percentage alternation behaviour in the Y-maze test indicating memory impairment which was ameliorated by kolaviron in a dose-dependent manner. Also, pre-training treatment with kolaviron significantly improved spatial learning evidenced in the session-dependent and more efficient localization of the hidden platform in the MWM test. Moreover, scopolamine injection induced significant increase in lipid peroxidation (prefrontal cortex), nitrite generation (striatum and hippocampus) and a decrease in glutathione (prefrontal cortex, striatum and hippocampus) and superoxide dismutase (striatum and hippocampus) level which was attenuated by kolaviron pre-treatment. These findings showed that kolaviron possesses cognition enhancing effect through enhancement of antioxidant defense and cholinergic systems.

Anti-Amnesic Effect of Fermented Ganoderma lucidum Water Extracts by Lactic Acid Bacteria on Scopolamine-Induced Memory Impairment in Rats.

This study investigated the anti-amnesic effect of fermented Ganoderma lucidum water extracts (GW) on scopolamine-induced memory impairment in rats. GW were fermented by the lactic acid bacterium Bifidobacterium bifidum (FGWB), followed by Lactobacillus sakei LI033 (FGWBL). To induce amnesia, scopolamine (1 mg/kg) was intraperitoneally injected into rats 30 min before the behavioral tests. Step-through latencies of rats treated with primary fermented extracts (300 mg/kg, FGWB) and secondary fermented extracts (300 mg/kg, FGWBL) were significantly longer than those of rats treated with GW (300 mg/kg) in the retention trial of the multiple trial passive avoidance test. In the Morris water maze task, FGWBL significantly shortened escape latencies in training trials. Furthermore, swimming times within the target zone during the probe trial with FGWBL were significantly higher than the GW and FGWB treatments. In addition, acetylcholinesterase activities were lower in the brains of scopolamine-treated rats treated with FGWBL. These results suggest that FGWBL could be useful to enhance learning memory and cognitive function via cholinergic dysfunction.

Ameliorative effect of rosmarinic acid on scopolamine-induced memory impairment in rats

Rosmarinic acid (RA) is a natural phenol that exerts different biological activities, such as antioxidant activity and neuroprotective effects. In this study, we hypothesized that administration of RA (8, 16, and 32mg/kg, p.o.) for 7 days would effect on scopolamine-induced cognitive dysfunction as an extensively used model of cognitive impairment.The rats were divided into 10 groups. The acquisition trial was done 1h after the last administration of RA. Animals were divided into control, RA (8, 16, and 32mg/kg) and donepezil (2mg/kg) treated controls, scopolamine, RA (8, 16, and 32mg/kg), and donepezil (2mg/kg) treated scopolamine groups. Memory impairment was induced by scopolamine treatment (1mg/kg, i.p.) 30min after the administration of RA, donepezil, or saline.Scopolamine administration caused cognition deficits in the PAL and memory paradigm. While orally RA administration (16 and 32mg/kg) improved learning and memory in control rats, it reversed learning and memory deficits of scopolamine received groups.Administration of RA at the dose of 8mg/kg did not alter cognitive function in control and scopolamine treated groups. The combination of anticholinesterase, neuroprotective, and antioxidant properties of RA may all be responsible for the observed effects. These results indicate the beneficial effects of subchronic RA administration in passive avoidance learning and memory in control rats as well as in a pharmacological model of cholinergic deficit which continue to expand the knowledge base in creating new treatment strategies for cognition deficits and dementia. Of course, further studies are warranted for clinical use of RA in the management of demented subjects.

Decaffeinated coffee prevents scopolamine-induced memory impairment in rats

IntroductionSeveral human studies have reported that coffee consumption improves cognitive performance. In the present study, we investigated whether instant decaffeinated coffee also ameliorates cognitive performance and attenuates the detrimental effects of scopolamine on memory. MethodsMemory performance was evaluated in Morris water maze test and passive avoidance test. Instant decaffeinated coffee (p.o.) at 120 or 240mg/kg in Sprague-Dawley rats, which is equivalent to approximately three or six cups of coffee, respectively, in a 60kg human, was administered for two weeks. ResultsOral gavage administration of instant decaffeinated coffee inhibited scopolamine-induced memory impairment, which was measured by Morris water maze test and passive avoidance test. Instant decaffeinated coffee suppressed scopolamine-mediated elevation of tumor necrosis factor-α (TNF-α) and stimulation of nuclear factor-κB (NF-κB) pathway (i.e., phosphorylation of IκBα and p65) in the rat hippocampus. DiscussionThese findings suggest that caffeine-free decaffeinated coffee may prevent memory impairment in human through the inhibition of NF-κB activation and subsequent TNF-α production.

Effects of Vitexin on Scopolamine-Induced Memory Impairment in Rats

Various synthetic derivatives of natural flavonoids are known to have neuroactive properties. The present study aimed to investigate the effects of vitexin (5, 7, 4-trihydroxyflavone-8-glucoside), a flavonoid found in such plants as tartary buckwheat sprouts, wheat leaves phenolome, Mimosa pudica Linn and Passiflora spp, on scopolamine-induced memory impairment in rats. To achieve this goal, we assessed the effects of vitexin on memory retrieval in the presence or absence of scopolamine using a step-through passive avoidance trial. In the first part of the study, vitexin (25, 50, and 100 microM) was administered intracerebroventricularly (i.c.v.) before acquisition trials. In the second part, vitexin, at the same doses, was administered before scopolamine (10 microg, i.c.v.) and before the acquisition trials. During retention tests, vitexin (100 microM) in the absence of scopolamine significantly increased the step-through latencies compared to scopolamine. In addition, vitexin (100 microM) significantly reversed the shorter step-through latencies induced by scopolamine (P < 0.05). These results indicate that vitexin has a potential role in enhancing memory retrieval. A possible mechanism is modulation of cholinergic receptors; however, other mechanisms may be involved in its effects in acute exposure.

Effect of Nigella sativa and wheat germ oils on scopolamine-induced memory impairment in rats

AimTo investigate the possible memory enhancing effects of Nigella sativa oil (NSO) and wheat germ oil (WGO) on scopolamine-induced amnesic rats. MethodsMale Wistar rats received either saline or scopolamine (16mg/kg, i.p.). The other three groups were pretreated with NSO (1ml/kg, p.o.), WGO (170mg/kg, p.o.) or donepezil used as a reference drug (10mg/kg, p.o.) for 14days before scopolamine injection. Cognitive and biochemical measurements were then assessed. Principal resultsNSO and WGO treated rats significantly reversed scopolamine-induced deficit of spatial and non-spatial working memory impairment in the T maze alternation task and object recognition test, respectively. Administration of NSO prior to scopolamine showed a significant decrease in malondialdehyde (MDA) and increase in Glutathione (GSH) brain contents to be similar to that observed in donepezil group. It did not alter cholinesterase activity and showed a significant decrease in brain tumor necrosis factor-alpha (TNF-α) content to be similar to donepezil-treated rats.Scopolamine-demented rats pretreated with WGO did not change MDA brain content significantly as compared to scopolamine and donepezil groups. WGO-treated rats showed a significant increase in GSH to a level similar to that observed in the donepezil group, it showed a significant decrease in cholinesterase activity as compared to scopolamine group and significantly elevated brain TNF-α content when compared to donepezil group. ConclusionsMemory enhancing effect of NSO in the present study might be due to its antioxidant and anti-inflammatory activities, while that of WGO might be via its antioxidant and anticholinesterase activities.

Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms

In this study we evaluated the effect of a novel, marine-derived, acidic oligosaccharide on scopolamine-induced amnesia in rats using the Morris water maze test. The results show that 30-day administration of this oligosaccharide, referred to as acidic oligosaccharide sugar chain (AOSC), to rats attenuates memory impairment by scopolamine, as evaluated by shortened escape latency, swimming distance, and increased swimming time of rats with memory impairment induced by scopolamine in the quadrant where the platform is placed. The data additionally suggest that an appropriate dose of scopolamine, a traditional muscarinic receptor antagonist, elevates oxidative damage in brain, characterized by inactivation of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and consequently, inhibition of ATPase in the hippocampus and cerebral cortex. AOSC ameliorates oxidative injuries caused by scopolamine by increasing the activities of SOD, GSH-Px, and ATPase. Further investigation by flow cytometry revealed that AOSC significantly reduces the overloading of intracellular free calcium ion ([Ca 2+] i), thus suppressing apoptosis induced by H 2O 2 in human neuroblastoma SH-SY5Y cells. These findings suggest that AOSC can induce cognitive improvement via its antioxidant activity.

Evidence for the involvement of the muscarinic cholinergic system in the central actions of pentoxifylline.

This study shows that pentoxifylline (ptx), a xanthine derivative, significantly attenuates scopolamine-induced memory impairment in rats, as demonstrated in a passive avoidance task (50 mg/kg intraperitoneally [i.p.]) and in an elevated T-maze (10 and 50 mg/kg i.p.). Ptx (25, 50 and 100 mg/kg i.p.) also potentiates oxotremorine-induced tremors in mice, in a dose-dependent manner, and this effect was completely prevented by atropine. In addition, ptx (50 and 100 mg/kg i.p.) increased the number of animals developing pilocarpine-induced seizures, and potentiated the latency to the first pilocarpine-induced convulsion. Hippocampus homogenates from rats treated with ptx (100 mg/kg) for 1 week and sacrificed 15 min after the last injection showed a significant decrease in the muscarinic receptor numbers, indicative of a downregulation phenomenon. Similar effects were observed when assays were performed 24 h after the last ptx injection (10 and 50 mg/kg i.p.), but not after 72 h. Additionally, in vitro assays showed that ptx inhibits acetylcholinesterase activity in a dose-dependent manner when incubated with homogenates from rat hippocampus. Our data suggest that the muscarinic agonist effect of ptx could possibly depend on factors such as endogenous cholinergic activity.

Effect of rivastigmine on scopolamine-induced memory impairment in rats

The effect of rivastigmine on memory impairments induced in rats by scopolamine (0.5 mg/kg) was assessed in the Morris water maze and passive avoidance tests and compared with that of tacrine (2.5–17.7 mg/kg). Rivastigmine, (0.5–2.5 mg/kg) inhibited cholinesterase in the cortex and hippocampus by 21–60% and antagonised the deficits in working and reference memory. Tacrine (12.5 and 17.7 mg/kg) produced significantly less inhibition of cholinesterase in the hippocampus but more in the striatum than rivastigmine (0.75 and 1.5 mg/kg) and only antagonised the deficit in reference memory. Rivastigmine (1.5 and 2.5 mg/kg) or tacrine (12.5 mg/kg), injected immediately after completion of the acquisition trial in the passive avoidance test, antagonised the deficit induced by scopolamine (1 mg/kg) in memory retention. The inability of higher doses of the cholinesterase inhibitors to antagonise memory deficits induced by scopolamine may be related to excessive cholinergic stimulation in the central nervous system.

Partial M1 but not M3 muscarinic agonists reverse scopolamine-induced memory impairment in rats : J. Blosser, D.V. Widzowski, P. Bialobok, K. Kucera, S. Sitar, S. McCreedy, A. Machulskis, G. Mullen, E. Wu, R. Murray, J. Gordon. Depts. Biology and Chemistry, Fisons Pharmaceuticals, Rochester, NY 14623

Partial M1 but not M3 muscarinic agonists reverse scopolamine-induced memory impairment in rats : J. Blosser, D.V. Widzowski, P. Bialobok, K. Kucera, S. Sitar, S. McCreedy, A. Machulskis, G. Mullen, E. Wu, R. Murray, J. Gordon. Depts. Biology and Chemistry, Fisons Pharmaceuticals, Rochester, NY 14623