Scopolamine In Rats Research Articles

Fustin, a Potent Phytochemical, Attenuates Scopolamine-induced Memory Impairment and Neurodegeneration by Modulating Neuroinflammation and Neurotransmitters.

Fustin, a photogenic flavanol found in the plant Rhus verniciflua Stokes, has been involved in multiple disease ailments and has a beneficial pharmacological effect and a history of use in traditional medicine. The present research aimed to study the impact of fustin on scopolamine (SCOP)-induced memory impairment and neurodegeneration by modulating neuroinflammation and neurotransmitters in rats. A total of 30 healthy Wistar rats were allocated into five groups (n=6). Group I- served as control and received saline solution (1mL/kg i.p.), group -II- fustin (100 mg/kg, orally), group -III -SCOP (1 mg/kg, i.p.), and group -IV and V were given fustin (50 and 100 mg/kg/p.o.) with SCOP (1 mg/kg, i.p.) for 14-days. After 14 days, 2 hours after SCOP injection, the Y-maze and Morris water maze (MWM) tests were performed. After behavioral tests rats were subsequently euthanized, and brain supernatants were used to estimate choline-acetyltransferase (ChAT), acetylcholinesterase (AChE), antioxidant [superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH)], and total protein, oxidative stress markers [nitrate and malondialdehyde (MDA)], pro-inflammatory markers [tumor necrosis factor (TNF-α), and Interleukins-1β (IL-1β) and IL-6]. Also, neurotransmitters such as serotonin (5-HT), dopamine (DA), ϒ-amino butyric acid (GABA), acetylcholine (Ach), and noradrenaline (NA) contents were performed. Fustin exhibited substantial behavioral improvement in the Y-maze measures spontaneous alterations percentage (SA%) and decreased latency time following the acquisition and prolonged time spent in the probe trial in the MWM test. Moreover, fustin inhibits enhanced neuroinflammatory cytokines and oxidative stress markers and improves the neurotransmitters. The findings of this study suggest that fustin inhibits SCOP impact on cognitive abilities in rats. The present investigation demonstrates that fustin, a potent phytochemical, effectively mitigated the behavioral and physiological changes induced by SCOP in rats. This was primarily achieved by modulating the levels of inflammatory response and neurotransmitters.

Ameliorative effect of vanillic acid against scopolamine-induced learning and memory impairment in rat via attenuation of oxidative stress and dysfunctional synaptic plasticity

Alzheimer’s disease (AD) is characterized by cognitive impairment, loss of learning and memory, and abnormal behaviors. Scopolamine (SCOP) is a non-selective antagonist of muscarinic acetylcholine receptors that exhibits the behavioral and molecular hallmarks of AD. Vanillic acid (VA), a phenolic compound, is obtained from the roots of a traditional plant called Angelica sinensis, and has several pharmacologic effects, including antimicrobial, anti-inflammatory, anti-angiogenic, anti-metastatic, and antioxidant properties. Nevertheless, VA’s neuroprotective potential associated with the memory has not been thoroughly investigated. Therefore, this study investigated whether VA treatment has an ameliorative effect on the learning and memory impairment induced by SCOP in rats. Behavioral experiments were utilized to assess the learning and memory performance associated with the hippocampus. Using western blotting analysis and assay kits, the neuronal damage, oxidative stress, and acetylcholinesterase activity responses of hippocampus were evaluated. Additionally, the measurement of long-term potentiation was used to determine the function of synaptic plasticity in organotypic hippocampal slice cultures. In addition, the synaptic vesicles’ density and the length and width of the postsynaptic density were evaluated using electron microscopy. Consequently, the behavioral, biochemical, electrophysiological, and ultrastructural analyses revealed that VA treatment prevents learning and memory impairments caused by SCOP in rats. The study’s findings suggest that VA has a neuroprotective effect on SCOP-induced learning and memory impairment linked to the hippocampal cholinergic system, oxidative damage, and synaptic plasticity. Therefore, VA may be a prospective therapeutic agent for treating AD.

Aegle marmelos (L.) Leaf Extract Improves Symptoms of Memory Loss Induced by Scopolamine in Rats.

Alzheimer's disease (AD) is the most common neurodegenerative disease that results in memory impairment. Aegle marmelos (L.) Correa (AM) is used as a traditional medicine. AM leaves have the potential to inhibit acetylcholinesterase activity. This study used scopolamine to induce AD in rats. The aim of this study was to investigate the effects of AM leaf extract using this model. Motor and memory functions were tested by the motor activity and Morris water maze (MWM) tests, respectively. The density of the synaptophysin and dendritic spines in the CA1 were detected by immunofluorescence and Golgi impregnation, respectively. The hippocampal histology was reviewed by H&E staining. After the treatment, the latency times in the MWM tests of the AD groups reduced, while the motor activities showed no difference. The density of the synaptophysin of the AD groups increased after the treatments, and that of the dendritic spines also increased in all AD groups post-treatment. The hippocampal tissue also recovered. AM leaf extract can improve cognitive impairment in AD models by maintaining the presynaptic vesicle proteins and dendritic spines in a dose-dependent manner.

Effect of Cocos nucifera L. Water on Scopolamine-Induced Memory Impairment in the Wistar Rat

Memory loss is an important Alzheimer's disease indicator (AD) linked with hippocampal damage. Scopolamine (SCO) antagonizes muscarinic acetylcholine receptor (mAChR) whose effect is similar to AD symptoms. Cocos nucifera L. (coconut) water is a crucial biological fluid containing nutritional components, and consumed for its health benefits. This study investigated the effect of C. nucifera water on memory impairment caused by SCO in rats. Thirty-two male Wistar rats were divided into four groups (n=8): control (normal saline); SCO (1 mg/kg/i.p.), C. nucifera water (0.4 mL/20 g) + SCO (1 mg/kg/i.p.), and donepezil (5 mg/kg/i.p.)+ SCO (1 mg/kg/i.p.). The levels of acetylcholinesterase (AChE), brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), tumour necrosis factor (TNF-α), and cyclo-oxygenase-2 (Cox-2) were measured. Hippocampal histology was done. Utilizing GraphPad Prism for statistical analy-sis, pre-treatment with C. nucifera water and donepezil displayed higher (p<0.01) spontaneous alternation in the Y-maze, and decreased escape latency, increased entries and time spent in the target quadrant (p<0.01) of the Morris water maze compared to the SCO group. These pre-treatment also inhibited AChE activity (p<0.001), and reduced expressions of IL-6, TNF-α and Cox-2 (p<0.001). However, there were no marked differences (p>0.05) in BDNF across the groups. Histology of SCO-only group revealed degenerated neurons, whereas the pre-treated groups showed regenerated neurons with less necrotic cells. The administration of SCO to the rats resulted in some form of memory impairment, and C. nucifera water showed promise for reversing this deficits

Determination of Scopolamine Distribution in Plasma and Brain by LC-MS/MS in Rats.

Scopolamine, as a tropane alkaloid found in plants such as belladonna and datura, is used clinically as a transdermal patch and is highly neurotoxic. This study aimed to develop a simple, sensitive, and selective LC-MS/MS method for the determination of the content and distribution of scopolamine in rat plasma and brain after drug administration. In our study, sample pretreatment consisted of protein precipitation with acetonitrile followed by nitrogen blow concentration. Gradient elution of scopolamine and internal standard was performed on a ZORBAX Eclipse Plus C18 (2.1∗100 mm, 3.5 μm) column with water containing 0.1% formic acid (v/v) and acetonitrile as a mobile phase. Those samples were quantified in ESI positive ion mode using an API 4000 triple quadrupole mass spectrometer. The results showed that scopolamine was linear in the calibration range of 2–2500 ng/mL, and the selectivity, accuracy, precision, matrix effect, stability, and recovery of the method were within acceptable limits. The method has been validated and has been successfully used for toxicokinetic studies of scopolamine. After intraperitoneal injection, the time to peak toxic concentrations of scopolamine in rats was 0.5 h. The concentrations of scopolamine in the hippocampus and cortex were much higher than those in the striatum, indicating that the likely targets of its neurotoxic damage were the hippocampus and cortex. Overall, this study provides the basis for the neurotoxicity of scopolamine and provides a reference for its toxicokinetic studies.

Consumption of Ashtanga Ghrita (clarified cow butter added with herb extracts) improves cognitive dysfunction induced by scopolamine in rats via regulation of acetylcholinesterase activity and oxidative stress.

Ashtanga Ghrita (AG), an Indian traditional formulation, has been used to promote neuropharmacological activities. AG is made up of clarified cow butter (ghee) and eight different herbs. To test whether scopolamine (SCP)-induced dementia and brain oxidative stress can be counteracted by AG, rats were separated into five groups (n=6/group): group one control, group two SCP (1mg/kg b.w., i.p.) treated and group three to five were co-treated with different doses of AG (1.25, 2.5 and 5g/kg b.w., orally) and SCP. After the treatment regimen, behavioral (Y-maze test) and brain biochemical changes were measured in all groups. Microbial load and heavy metals were found within permissible limits. Results from attenuated total reflection Fourier-transform infrared spectroscopy demonstrated the complexation/interaction of herbal phytoconstituents with the functional groups of Ghrita. Preliminary phytochemical analysis of AG exhibited the occurrence of flavonoids, phenolics, glycosides, steroids, triterpenes, tannins, and amino acids. Findings of the experimental study exhibited that AG significantly protected the rats from SCP-induced behavioral dysfunction and brain biochemical alterations. This study demonstrates that AG protects the brain from SCP-induced dementia by promoting brain antioxidant activity and thus could be a promising drug for the treatment of neurodegenerative disease.

EFFECT OF DROTAVERINE, A PHOSPHODIESTERASE 4 INHIBITOR IN SCOPOLAMINE-INDUCED COGNITIVE IMPAIRMENT IN RATS

Objective: Cognitive impairment (CI) is a progressive neurodegenerative disorder and causes significant dementia in the elderly. Intracellular cyclic AMP (cAMP) signaling has been well established in the mediation of memory. Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cAMP and/or cyclic GMP. Drotaverine is a novel non-anticholinergic smooth muscle antispasmodic which acts by inhibiting PDE-4. It is now clinically used in smooth muscle spasms (intestinal, biliary and renal colic, irritable bowel syndrome, uterine spasms, etc.) without anticholinergic side effects. Since Drotaverine has PDE4 inhibition property, its role in learning and memory was evaluated in this study and found that it has memory enhancing effect comparable with donepezil in scopolamine-induced CI in rats.
 Methods: Learning and memory were assessed with two behavioral models, namely, elevated plus maze (EPM) and Y maze. CI was produced by scopolamine. Rats were divided into five groups, Group I treated with normal saline, Group II treated with scopolamine, and Groups III, IV, and V were treated with donepezil, Drotaverine, and both, respectively.
 Results: The result analysis revealed significant differences in transfer latency in EPM performance between Groups III, IV, V and Group II (***p<0.001). The results of spontaneous alternation in Y maze show that there was a significant difference among all the treatments groups (p<0.001).
 Conclusion: Drotaverine has promising memory enhancing effect in CI induced by scopolamine in rats. Further clinical trials are needed to prove this finding which has been elicited in animal models.

Influence of cooking on the neuroprotective properties of pepper (bird pepper and cayenne pepper) varieties in scopolamine‐induced neurotoxicity in rats

This study investigated the influence of cooking on the neuroprotective property of two pepper varieties in the rat model of amnesia. Rats were pre-treated with dietary inclusions of 2% Bird pepper (BP) and Cayenne pepper (CP) (raw and cooked [for 30 min at 100 ± 0.5°C]) for 21 days, after which neurotoxicity was induced by scopolamine. Thereafter, the spatial working memory of the rats was evaluated, and the brain tissue was assayed for the activities of acetylcholinesterase and ecto-nucleotidases, as well as lipid peroxidation. Furthermore, the ascorbic acid, carotenoid, and capsinoid levels of the peppers were determined. The result showed that dietary inclusions of BP and CP significantly ameliorated behavioral and biochemical impairments induced by scopolamine in rats; however, cooked peppers showed no significant difference compared to raw. Furthermore, the bioactive contents were preserved by cooking. This study, therefore, revealed that the neuroprotective effects of the peeper varieties were conserved by cooking. Novelty Impact Statement Cooking is one of the culinary practices used in food processing and preservation. This method often produces varying effects on the bioactive constituents of functional foods, hence, it is important to consider. Pepper varieties have been reported for their neuroprotective properties, but with a dearth of information on how culinary practices could affect this therapeutic effect. Therefore, in this study, we investigated the influence of cooking, one of the main culinary practices of pepper varieties, on some behavioral and biochemical indices in scopolamine neurotoxic rats.

A dual-acting 5-HT6 receptor inverse agonist/MAO-B inhibitor displays glioprotective and pro-cognitive properties.

The complex etiology of Alzheimer's disease has initiated a quest for multi-target ligands to address the multifactorial causes of this neurodegenerative disorder. In this context, we designed dual-acting 5-HT6 receptor (5-HT6R) antagonists/MAO-B inhibitors using pharmacophore hybridization strategy. Our approach involved linking priviliged scaffolds of 5-HT6R with aryloxy fragments derived from reversible and irreversible MAO-B inhibitors. The study identified compound 48 that acts as an inverse agonist of 5-HT6R at Gs signaling and an irreversible MAO-B inhibitor. Compound 48 showed moderate metabolic stability in rat microsomal assay, artificial membrane permeability, no hepatotoxicity, and it was well distributed to the brain. Additionally, 48 showed glioprotective properties in a model of cultured astrocytes using 6-OHDA as the cytotoxic agent. Finally, compound 48 (MED=1mg/kg, p.o.) fully reversed memory deficits in the NOR task induced by scopolamine in rats. A better understanding of effects exerted by dual-acting 5-HT6R/MAO-B modulators may impact the future development of neurodegenerative-directed treatment strategies.

2-Aminoimidazole-based antagonists of the 5-HT6 receptor – A new concept in aminergic GPCR ligand design

A new strategy in the design of aminergic GPCR ligands is proposed – the use of aromatic, heterocyclic basic moieties in place of the evergreen piperazine or alicyclic and aliphatic amines. This hypothesis has been tested using a benchmark series of 5-HT6R antagonists obtained by coupling variously substituted 2-aminoimidazole moieties to the well established 1-benzenesulfonyl-1H-indoles, which served as the ligands cores. The crystallographic studies revealed that upon protonation, the 2-aminoimidazole fragment triggers a resonance driven conformational change leading to a form of higher affinity. This molecular switch may be responsible for the observed differences in 5-HT6R activity of the studied chemotypes with different amine-like fragments. Considering the multiple functionalization sites of the embedded guanidine fragment, diverse libraries were constructed, and the relationships between the structure and activity, metabolic stability, and solubility were established. Compounds from the N-(1H-imidazol-2-yl)acylamide chemotype (10a–z) exhibited high affinity for 5-HT6R and very high selectivity over 5-HT1A, 5-HT2A, 5-HT7 and D2 receptors (negligible binding), which was attributed to their very weak basicity. The lead compound in the series 4-methyl-5-[1-(naphthalene-1-sulfonyl)-1H-indol-3-yl]-1H-imidazol-2-amine (9i) was shown to reverse the cognitive impairment caused by the administration of scopolamine in rats indicating procognitive potential.

Mitochondrial involvement in memory impairment induced by scopolamine in rats

Objective: Scopolamine (SCO) administration to rats induces molecular features of AD and other dementias, including impaired cognition, increased oxidative stress, and imbalanced cholinergic transmission. Although mitochondrial dysfunction is involved in different types of dementias, its role in cognitive impairment induced by SCO has not been well elucidated. The aim of this work was to evaluate the in vivo effect of SCO on different brain mitochondrial parameters in rats to explore its neurotoxic mechanisms of action.Methods: Saline (Control) or SCO (1 mg/kg) was administered intraperitoneally 30 min prior to neurobehavioral and biochemical evaluations. Novel object recognition and Y-maze paradigms were used to evaluate the impact on memory, while redox profiles in different brain regions and the acetylcholinesterase (AChE) activity of the whole brain were assessed to elucidate the amnesic mechanism of SCO. Finally, the effects of SCO on brain mitochondria were evaluated both ex vivo and in vitro, the latter to determine whether SCO could directly interfere with mitochondrial function.Results: SCO administration induced memory deficit, increased oxidative stress, and increased AChE activities in the hippocampus and prefrontal cortex. Isolated brain mitochondria from rats administered with SCO were more vulnerable to mitochondrial swelling, membrane potential dissipation, H2O2 generation and calcium efflux, all likely resulting from oxidative damage. The in vitro mitochondrial assays suggest that SCO did not affect the organelle function directly.Conclusion: In conclusion, the present results indicate that SCO induced cognitive dysfunction and oxidative stress may involve brain mitochondrial impairment, an important target for new neuroprotective compounds against AD and other dementias.

Combined treatment with pantothenic acid derivatives and memantine alleviates scopolamine-induced amnesia in rats: The involvement of the thiol redox state and coenzyme A

Free-radical-mediated processes are involved in a variety of physiological events, while oxidative stress and related redox deregulation are implicated in various pathological events. Tripeptide glutathione plays an important role in the antioxidant defense of the brain, particularly in the maintenance of the optimal redox state in neurons and glial cells. We studied the combined effects of pantothenic acid derivatives, pantothenol and calcium pantothenate, and memantine, which is a glutamate receptor antagonist that is widely used for the treatment of dementia, on amnesia induced by scopolamine in rats. Scopolamine induced amnesia in rats; however, unexpectedly, this effect was even more expressed in the memantine-pretreated animals. Memory impairments were less manifested in the rats that were pretreated with memantine in combination with panthenol or calcium pantothenate. The detrimental scopolamine effect on memory was accompanied by significant depletions of glutathione and coenzyme A in the brain. While memantine recovered the glutathione status to some extent, it nevertheless further aggravated the scopolamine influence on coenzyme A levels. An alleviation of scopolamine-induced memory impairments that was observed after combined pretreatment with memantine and panthenol or calcium pantothenate was accompanied by a normalization of coenzyme A levels, while the effects on glutathione redox did not correlate with the behavioral data.

Inhibitory effect of Thymus vulgaris extract on memory impairment induced by scopolamine in rat

ObjectiveTo investigate the effect of Thymus vulgaris (T. vulgaris) on learning and memory functions in scopolamine-induced memory deficit in rats. Memory enhancing activity in scopolamine-induced amnesic rats was investigated by assessing the Morris water maze and passive avoidance paradigm. MethodsA total of 42 male Wistar rats were divided into 6 equal groups as follow: control group: received water, scopolamine treated group: received scopolamine 1 mg/kg for 15 days, two scopolamine + T. vulgaris treated groups: received scopolamine and T. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days, two intact groups: received T. vulgaris extract 50 and 100 mg/kg body weight per day for 15 days. ResultsAdministration of T. vulgaris extract significantly restored memory and learning impairments induced by scopolamine in the passive avoidance test and Morris water maze test. ConclusionsT. vulgaris extract has repairing effects on memory and behavioral disorders produced by scopolamine and may have beneficial effects in the treatment of Alzheimer's disease.

Effects of Matricaria chamomilla extract on motor coordination impairment induced by scopolamine in rats

ObjectiveTo evaluate the effect of ethanolic extract of chamomile on balance and motor learning in rats receiving scopolamine and intact rats. MethodsFourty-two rats were divided into 6 groups (n = 7). Control group received distilled water. Rats in Group 2 were given 1 mg/kg scopolamine. Groups 3 and 4 received chamomile extract 200 mg/kg and 500 mg/kg, respectively, and scopolamine simultaneously for 20 days. Intact groups (Groups 5 and 6) only received chamomile extract 200 mg/kg and 500 mg/kg, respectively. Motor coordination of rats was assessed with rotarod apparatus. ResultsAccording to the obtained results, compared with the control group, scopolamine significantly decreased time spent on rotarod performance (P < 0.001). Compared with scopolamine group, the strength and staying on rotarod apparatus in Group 3 significantly increased (P < 0.05). The results of this research showed that intact groups that received only chamomile extract at doses of 200 mg/kg and 500 mg/kg significantly increased time spent on rotarod, compared with scopolamine group (P < 0.001). ConclusionsThe results of this study indicated the high antioxidant property and protective effect of chamomile extract on motor coordination in the groups that received scopolamine.

Evaluation of Cucurbita maxima extract against scopolamine-induced amnesia in rats: implication of tumour necrosis factor alpha.

Cucurbita maxima (CM) seed oil is commonly used in Indian folk medicine to treat various ailments. We have investigated the effect of CM seed oil on memory impairment induced by scopolamine in rats. Male adult Wistar rats were administered scopolamine 1 mg/kg body weight, i.p. or 1.25 mg/kg body weight, s.c. to induce memory impairment. The nootropic agent piracetam 100 mg/kg body weight, i.p. and CM seed oil 100 and 200 mg/kg body weight, p.o. were administered daily for five consecutive days. The memory function was evaluated in the Morris water maze (MWM) test, the social recognition test (SRT), the elevated plus maze (EPM) test, and the pole climbing test (PCT). Acetylcholinesterase (AChE) activity and oxidative stress parameters were estimated in the cortex, hippocampus, and cerebellum of the brains after completion of the behavioural studies. The effects of scopolamine on the levels of the tumour necrosis factor alpha (TNF-α) transcript were also investigated. Scopolamine caused memory impairment in all the behavioural paradigms along with a significant increase in the AChE activity and oxidative stress in the brain. Scopolamine also caused a significant increase in the expression of TNF-α in the hippocampus. CM seed oil exhibited antiamnesic activity as indicated by a significant reduction in the latency time in the MWM test and decreased social interaction during trial 2 in the SRT. Further, treatment with CM seed oil significantly decreased the AChE activity and malondialdehyde levels and increased the glutathione level in brain regions. CM seed oil also significantly decreased the expression of TNF-α in the hippocampus. The effect of CM seed oil on behavioural and biochemical parameters was comparable to that observed in rats treated with piracetam. These results indicate that CM seed oil may exert antiamnesic activity which may be attributed to the inhibition of AChE and inflammation as well as its antioxidant activity in the brain.

Dorsolateral frontal cortex and peripheral muscarinic receptors participation in the discriminative stimulus properties of scopolamine in rats

Organisms are capable of making decisions based on their ability to discriminate between different stimuli. This principle is fundamental for the adaptation of organisms to their environment, by emitting appropriate behaviors based on a previously acquired discriminative process. The present study analyzed the participation of the peripheral nervous system, the M1 muscarinic receptor subtype, as well as the contribution of the dorsolateral frontal cortex to discrimination process using scopolamine as discriminative stimulus.Male Wistar rats were trained to discriminate between scopolamine (1.0mg/kg) and saline injections (i.p.) using a two-lever operant procedure. Once discrimination was acquired, generalization curves for scopolamine, methylscopolamine, pirenzepine, dorsolateral frontal cortex lesion and control conditions were obtained.Results showed that rats were able to discriminate and generalize its responses to different doses of scopolamine but not for methylscopolamine or pirenzepine, thus the data suggest that discriminative properties of scopolamine are processed in CNS and that the M1 receptor does not participate in this process. Dorsolateral frontal cortex lesion did not produce any statistically significant difference in the generalization curve, which suggests that a system different from the dorsolateral prefrontal cortex may be responsible for the control of stimulus produced by scopolamine.

Combination Effects of ZSET1446/ST101 With Memantine on Cognitive Function and Extracellular Acetylcholine in the Hippocampus

In the novel object recognition task, ZSET1446 (also coded as ST101) enhanced object recognition memory in mice and ameliorated cognitive impairment caused by scopolamine in rats. The enhancement induced by ZSET1446 in mice was abolished by injection of mechamylamine, a nonselective antagonist of nicotinic acetylcholine (ACh) receptors, or dihydro-β-erythroidine, a selective antagonist against the α4 subunit of nicotinic ACh receptors. These results suggest that the procognitive effect of ZSET146 is probably mediated by stimulation of nicotinic receptors. Memantine was also effective in these tests and concomitant administration of subeffective doses of ZSET1446 and memantine significantly ameliorated the cognitive performance in the novel object recognition task in both mice and rats. Moreover, oral administration of ZSET1446 or memantine increased the extracellular level of ACh in the hippocampus as compared with the control. Further, concomitant administration of subeffective doses of ZSET1446 and memantine significantly increased the extracellular level of ACh as compared with the group of ZSET1446 or memantine alone. These results suggest that these two compounds have a synergistic effect on the cognitive function possibly by synergistic increase in the extracellular level of ACh in the hippocampus, and that the combination therapy of these compounds might be effective in clinical settings.

Fucoidan ameliorates scopolamine-induced neuronal impairment and memory dysfunction in rats via activation of cholinergic system and regulation of cAMP-response element-binding protein and brain-derived neurotrophic factor expressions

Effect of fucoidan (FCN) treatment on improving memory defects caused by administration of scopolamine (SCO) to the rats was examined. The effects of FCN on the acetylcholinergic system as well as the expression of cAMP-response elementbinding protein (CREB) and brain-derived neurotrophic factor (BDNF) mRNAs in the hippocampus were also investigated. Male rats were administered daily doses for 14 days of FCN (10, 20, and 50 mg/kg, i.p.) 30 min before scopolamine injection (2 mg/kg, i.p.). Daily administration of FCN improved memory impairment as measured by the passive avoidance test (PAT) and reduced the escape latency for finding the platform in the Morris water maze (MWM) test. Administration of FCN significantly alleviated memory-associated decreases in cholinergic immunoreactivity and restored the expression level of BDNF and CREB mRNAs in the hippocampus. Additionally, FCN significantly decreased the expression of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mRNAs in the hippocampus. These results demonstrated that FCN has significant neuroprotective effects against neuronal impairment and memory dysfunction caused by scopolamine in rats. Thus, these findings suggest that FCN is useful as a therapeutic agent for improving cognitive functioning via stimulation of cholinergic enzyme activities and regulation of CREB and BDNF expressions in the brain.

Anxiolytic effects of environmental enrichment attenuate sex-related anxiogenic effects of scopolamine in rats

In groups of four same-sexed animals, PVG/c hooded rats were housed for 4.5 months in standard or enriched cages containing several objects that could be explored and manipulated. On separate occasions, each rat then experienced two consecutive daily trials in an open field, a light-dark box or a Y maze with arm inserts that enabled an acquisition trial comprising one black and one white arm to be changed for a retention trial consisting of two black arms. Before their trials in the open field and light-dark box, and following each acquisition trial in the Y maze, the rats received an intraperitoneal injection of 2 mg/kg scopolamine or isotonic saline. In the open field, enrichment led to higher levels of ambulation, walking, rearing and occupancy of the center of the apparatus and shorter emergence latencies from the dark into the light compartment of the light-dark box accompanied by more entries of this compartment. Enrichment also increased entries of and time spent in the changed (or novel) Y-maze arm only for male rats treated with scopolamine. The drug decreased rearing and increased grooming in the open field as well as increasing emergence latencies and decreasing entries of and the time spent on the light compartment of the light-dark box. The main results were interpreted as enrichment having attenuated anxiogenic effects of the behavioral testing and the action of scopolamine for male (but not female) rats in their choices of the novel arm in the Y maze.

P1‐290: Pharmacokinetic‐pharmacodynamic relationships of amnesic effects of scopolamine in rats

P1‐290: Pharmacokinetic‐pharmacodynamic relationships of amnesic effects of scopolamine in rats