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  1. Khleifat KM, Al-Tawarah NM, Al-Kafaween MA, Al-Ksasbeh W, Qaralleh H, Alqaraleh M, et al.
    Curr Alzheimer Res, 2023;20(3):190-201.
    PMID: 37317907 DOI: 10.2174/1567205020666230614143027
    BACKGROUND/OBJECTIVE: Alzheimer's disease (AD) is mainly characterized by amnesia that affects millions of people worldwide. This study aims to explore the effectiveness capacities of bee venom (BV) for the enhancement of the memory process in a rat model with amnesia-like AD.

    METHODS: The study protocol contains two successive phases, nootropic and therapeutic, in which two BV doses (D1; 0.25 and D2: 0.5 mg/kg i.p.) were used. In the nootropic phase, treatment groups were compared statistically with a normal group. Meanwhile, in the therapeutic phase, BV was administered to scopolamine (1mg/kg) to induce amnesia-like AD in a rat model in which therapeutic groups were compared with a positive group (donepezil; 1mg/kg i.p.). Behavioral analysis was performed after each phase by Working Memory (WM) and Long-Term Memory (LTM) assessments using radial arm maze (RAM) and passive avoidance tests (PAT). Neurogenic factors; Brain-derived neurotrophic factor (BDNF), and Doublecortin (DCX) were measured in plasma using ELISA and Immunohistochemistry analysis of hippocampal tissues, respectively.

    RESULTS: During the nootropic phase, treatment groups demonstrated a significant (P < 0.05) reduction in RAM latency times, spatial WM errors, and spatial reference errors compared with the normal group. In addition, the PA test revealed a significant (P < 0.05) enhancement of LTM after 72 hours in both treatment groups; D1 and D2. In the therapeutic phase, treatment groups reflected a significant (P < 0.05) potent enhancement in the memory process compared with the positive group; less spatial WM errors, spatial reference errors, and latency time during the RAM test, and more latency time after 72 hours in the light room. Moreover, results presented a marked increase in the plasma level of BDNF, as well as increased hippocampal DCX-positive data in the sub-granular zone within the D1 and D2 groups compared with the negative group (P < 0.05) in a dose-dependent manner.

    CONCLUSION: This study revealed that injecting BV enhances and increases the performance of both WM and LTM. Conclusively, BV has a potential nootropic and therapeutic activity that enhances hippocampal growth and plasticity, which in turn improves WM and LTM. Given that this research was conducted using scopolamine-induced amnesia-like AD in rats, it suggests that BV has a potential therapeutic activity for the enhancement of memory in AD patients in a dose-dependent manner but further investigations are needed.

    Matched MeSH terms: Scopolamine Hydrobromide/adverse effects
  2. Khalid A, Shakeel R, Justin S, Iqbal G, Shah SAA, Zahid S, et al.
    Curr Drug Targets, 2017;18(13):1545-1557.
    PMID: 28302036 DOI: 10.2174/1389450118666170315120627
    BACKGROUND: Stress is involved in memory impairment through multiple mechanisms, including activation of hypothalamic-pituitary axis, which in turn activates release of corticosterone in blood. Cholinergic system blockade by the muscarinic antagonist, scopolamine, also impairs memory.

    OBJECTIVE: This study aimed to investigate the effect of turmeric (20mg/kg) on learning and memory and cholinergic system in a mouse model of stress along with cholinergic blockade.

    METHODS: Restrained stress was induced and cholinergic receptors were blocked using scopolamine in mice. Animals were treated with turmeric (turmeric rhizome powder which was also subjected to NMR analyses) and learning and social behavior was examined. Effect of turmeric on cholinergic muscarinic receptors (mAChR; M1, M3 and M5) gene expression was assessed by RT-PCR in both pre-frontal cortex and hippocampus.

    RESULTS: Ar-turmerone, curcuminoids and α-linolenic acid were the lead compounds present in turmeric extract. Increased serum corticosterone levels were observed in stressed mice when compared to the control group, while turmeric treatment significantly reduced serum corticosterone level. Turmeric treatment caused an improved learning and memory in Morris water maze test in stressed animals. Social novelty preference was also restored in turmeric treated animals. Following turmeric treatment, M5 expression was improved in the cortex and M3 expression was improved in the hippocampus of stress + scopolamine + turmeric treated group.

    CONCLUSIONS: These findings highlight the therapeutic role of turmeric by increasing the expression of M3, M5 and improving learning and memory. Turmeric can be an effective candidate for the treatment of amnesia caused by the stress.

    Matched MeSH terms: Scopolamine Hydrobromide/administration & dosage*; Scopolamine Hydrobromide/pharmacology
  3. Babiker, F., Jamal, P., Mirghani, M.E.S., Ansari, A.H.
    MyJurnal
    This study aimed at investigating the presence of alkaloids and other chemical constituents in Datura stramonium (Saikaran, Jimson weed). All parts of the plant were dried, crushed and then underwent extraction by soxhlet and maceration methods. The solvents used in these methods were normal hexane (nonpolar) and ethanol (polar). Thin Layer Chromatography (TLC) and FTIR techniques were used to analyse the chemical components of jimson weed. The results showed the presence of hyoscine in all plant parts while atropine in the seeds only. The best separation was found to be when the solvent system was acetone: water: ammonia (90:07:03). Maceration method is the best and cost effective procedure for extraction.
    Matched MeSH terms: Scopolamine Hydrobromide
  4. Mohd Fahmi Shukur Ramli, Fadzilah Hamzah, Muhamad Zabidi Ahmad
    MyJurnal
    Positron Emission Tomography-Computed Tomography (PET-CT) was introduced over four decades ago as an imaging tool to evaluate functional and anatomical aspects of disease such as malignancy. Besides pathological uptake, PET-CT also shows physiological uptake, especially in the gastrointestinal system, thus impacting diagnostic accuracy in these cases. There are many conditions that can attribute to increasing physiological uptake in PET-CT including microbial activity and drugs. Therefore, certain anti-spasmodic agents have been introduced to help reduce physiological uptake during scanning such as Hyoscine-n-butylbromide (Buscopan). This study aims to establish its effectiveness in reducing physiological bowel uptake on 18F-FDG PET-CT scan. Methods: 133 subjects were recruited in random for this study and divided into hyoscine (68 subjects) and control groups (65 subjects), respectively. Subjects in control group not given any anti-spasmodic medications and both groups received intravenous 18F-FDG according to body weight. PET-CT scan and images were interpreted by experienced nuclear medicine physician who scored the images according to the degree of bowel uptake and difficulty of image interpretation. Results: There were no statistical difference in bowel uptake based on SUV mean of the bowel and bowel-to-liver ratio between hyoscine and control groups. Conclusion: There was no significant effect of Hyoscine-n-butylbromide in reducing physiological bowel uptake in PET-CT scan.
    Matched MeSH terms: Scopolamine Hydrobromide
  5. Norazrina Azmi, Loh WT, Siti Suriani Omar, Juriyati Jalil, Aishah Adam
    Sains Malaysiana, 2011;40:1097-1103.
    The aqueous extract of Prismatomeris glabra root has been used traditionally in Malaysia by the aborigines and certain rural Malays for its ergogenic effects, to maintain wellness and to enhance physical stamina. It has also been used as an aphrodisiac for generations in the east coast of Peninsular Malaysia. Previous studies have shown that plants with ergogenic effects may also act as a stimulant and impair cognitive function. Therefore, we seek to investigate the effects of P. glabra on non-spatial memory in male Sprague Dawley rats using object recognition test. Trial rats were injected intraperitoneally with an aqueous extract of P. glabra roots at doses of 50 and 100 mg/kg for the acute (30 min) and subacute (7 days) studies. Scopolamine (0.3 mg/kg) was used as a positive control only in the acute study meanwhile control rats were injected with saline. The locomotor activity of rats was also determined in the same test. We demonstrated that groups treated with 50 and 100 mg/kg of the extract lost their ability to discriminate the novel from familiar object in choice phase and did not alter the locomotor activity in both studies. Our results also indicated that the deficits in non-spatial working memory occured at these doses were not due to impaired locomotor activity.
    Matched MeSH terms: Scopolamine Hydrobromide
  6. Apryani E, Hidayat MT, Moklas MA, Fakurazi S, Idayu NF
    J Ethnopharmacol, 2010 Jun 16;129(3):357-60.
    PMID: 20371280 DOI: 10.1016/j.jep.2010.03.036
    AIM OF THE STUDY: Mitragyna speciosa Korth from Rubiaceae family is a tropical plant indigenous to Southeast Asia particularly in Thailand, Peninsular of Malaysia and Indonesia. The leaves have been used by natives for their opium-like effect and cocaine-like stimulant ability to combat fatigue and enhance tolerance to hard work. However there is no scientific information about the effect of mitragynine on the cognitive performances. This study is designed to examine the working memory effects of mitragynine which is extracted from Mitragyna speciosa mature leaves.

    MATERIALS AND METHODS: The cognitive effect was studied using object location task and the motor activity in open-field test. Mitragynine 5, 10 and 15 mg/kg and were administered by intraperitoneal (IP) for 28 consecutive days and evaluated on day 28 after the last dose treatment. Scopolamine was used as the control positive drug.

    RESULTS: In this study there is prominent effects on horizontal locomotor activity was observed. Mitragynine significantly reduced locomotor activity in open-field test compared with vehicle. In object location task mitragynine (5, 10 and 15 mg/kg) did not showed any significances discrimination between the object that had changed position than the object that had remain in a constant position.

    CONCLUSION: Our results suggest that chronic administration of mitragynine can altered the cognitive behavioral function in mice.

    Matched MeSH terms: Scopolamine Hydrobromide/pharmacology
  7. Tang KS
    Life Sci, 2019 Sep 15;233:116695.
    PMID: 31351082 DOI: 10.1016/j.lfs.2019.116695
    Alzheimer's disease (AD) is neurodegenerative disorder that is associated with memory and cognitive decline in the older adults. Scopolamine is commonly used as a behavioral model in studying cognitive disorders including AD. Many studies have also concurrently examined the neurochemical mechanisms underlying the behavioral modifications by scopolamine treatment. Nonetheless, the scopolamine model has not become a standard tool in the early assessment of drugs. Furthermore, the use of scopolamine as a pharmacological model to study AD remains debatable. This report reviews the scopolamine-induced cellular and molecular changes and discusses how these changes relate to AD pathogenesis.
    Matched MeSH terms: Scopolamine Hydrobromide/adverse effects*
  8. Ahmad A, Ramasamy K, Jaafar SM, Majeed AB, Mani V
    Food Chem Toxicol, 2014 Mar;65:120-8.
    PMID: 24373829 DOI: 10.1016/j.fct.2013.12.025
    The present study was undertaken to compare the neuroprotective effects between total isoflavones from soybean and tempeh against scopolamine-induced cognitive dysfunction. Total isoflavones (10, 20 and 40mg/kg) from soybean (SI) and tempeh (TI) were administered orally to different groups of rats (n=6) for 15days. Piracetam (400mg/kg, p.o.) was used as a standard drug while scopolamine (1mg/kg, i.p.) was used to induce amnesia in the animals. Radial arm and elevated plus mazes served as exteroceptive behavioural models to measure memory. Brain cholinergic activities (acetylcholine and acetylcholinesterase) and neuroinflammatory activities (COX-1, COX-2, IL-1β and IL10) were also assessed. Treatment with SI and TI significantly reversed the scopolamine effect and improved memory with TI group at 40mg/kg, p.o. exhibiting the best improvement (p<0.001) in rats. The TI (10, 20 and 40mg/kg, p.o.) significantly increased (p<0.001) acetylcholine and reduced acetylcholinesterase levels. Meanwhile, only a high dose (40mg/kg, p.o.) of SI showed significant improvement (p<0.05) in the cholinergic activities. Neuroinflammation study also showed that TI (40mg/kg, p.o.) was able to reduce inflammation better than SI. The TI ameliorates scopolamine-induced memory in rats through the cholinergic neuronal pathway and by prevention of neuroinflammation.
    Matched MeSH terms: Scopolamine Hydrobromide/toxicity*
  9. Kan HW, Peng WH, Wu CC, Wang DW, Lee MT, Lee YK, et al.
    Psychopharmacology (Berl), 2022 Dec;239(12):3805-3818.
    PMID: 36221037 DOI: 10.1007/s00213-022-06250-1
    RATIONALE: Clinical reports reveal that scopolamine, an acetylcholine muscarinic receptor antagonist, exerts rapid antidepressant effects in depressed patients, but the mechanisms underlying the therapeutic effects have not been fully identified.

    OBJECTIVES: The present study examines the cellular mechanisms by which scopolamine produces antidepressant-like effects through its action in the ventrolateral midbrain periaqueductal gray (vlPAG).

    METHODS: We used a well-established mouse model of depression induced by chronic restraint stress (CRS) exposure for 14 days. Behaviors were tested using the forced swim test (FST), tail suspension test (TST), female urine sniffing test (FUST), novelty-suppressed feeding test (NSFT), and locomotor activity (LMA). Synaptic transmission in the vlPAG was measured by whole-cell patch-clamp recordings. IntravlPAG microinjection was used to pharmacologically verify the signaling cascades of scopolamine in the vlPAG.

    RESULTS: The results demonstrated that intraperitoneal injection of scopolamine produced antidepressant-like effects in a dose-dependent manner without affecting locomotor activity. CRS elicited depression-like behaviors, whereas intraperitoneal injection of scopolamine alleviated CRS-induced depression-like behaviors. CRS diminished glutamatergic transmission in the vlPAG, while scopolamine reversed the above effects. Moreover, intravlPAG microinjection of the L-type voltage-dependent calcium channel (VDCC) blocker verapamil, tropomyosin-related kinase B (TrkB) receptor antagonist ANA-12, mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin, and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) antagonist CNQX prevented scopolamine-induced antidepressant-like effects.

    CONCLUSIONS: Scopolamine ameliorated CRS-elicited depression-like behavior required activation of VDCC, resulting in activity-dependent release of brain-derived neurotrophic factor (BDNF), engaging the TrkB receptor and downstream mTORC1 signaling in the vlPAG.

    Matched MeSH terms: Scopolamine Hydrobromide/pharmacology
  10. Nasir MN, Habsah M, Zamzuri I, Rammes G, Hasnan J, Abdullah J
    J Ethnopharmacol, 2011 Mar 24;134(2):203-9.
    PMID: 21167268 DOI: 10.1016/j.jep.2010.12.010
    Centella asiatica has a reputation to restore declining cognitive function in traditional medicine. To date, only a few compounds that show enhancing learning and memory properties are available. Therefore, the present study investigates the effects of for acute administration of asiatic acid (A-A) isolated from Centella asiatica administration on memory and learning in male Spraque-Dawley rats.
    Matched MeSH terms: Scopolamine Hydrobromide/pharmacology
  11. Tee HP, Corte C, Al-Ghamdi H, Prakoso E, Darke J, Chettiar R, et al.
    World J Gastroenterol, 2010 Aug 21;16(31):3905-10.
    PMID: 20712051
    AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate.

    METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assisted colonoscopy (CAC) was performed after consent was obtained. For cases randomized to CAC, one of the three sizes of cap was used: D-201-15004 (with a diameter of 15.3 mm), D-201-14304 (14.6 mm) and D-201-12704 (13.0 mm). All of these caps were produced by Olympus Medical Systems, Japan. Independent predictors for faster cecal time and better polyp detection rate were also determined from this study.

    RESULTS: There were 200 cases in each group. There was no significant difference in terms of demographic characteristics between the two groups. CAC, when compared to the SC group, had no significant difference in terms of cecal intubation rate (96.0% vs 97.0%, P = 0.40) and time (9.94 +/- 7.05 min vs 10.34 +/- 6.82 min, P = 0.21), or polyp detection rate (32.8% vs 31.3%, P = 0.75). On the subgroup analysis, there was no significant difference in terms of cecal intubation time by trainees (88.1% vs 84.8%, P = 0.40), ileal intubation rate (82.5% vs 79.0%, P = 0.38) or total colonoscopy time (23.24 +/- 13.95 min vs 22.56 +/- 9.94 min, P = 0.88). On multivariate analysis, the independent determinants of faster cecal time were consultant-performed procedures (P < 0.001), male patients (P < 0.001), non-usage of hyoscine (P < 0.001) and better bowel preparation (P = 0.01). The determinants of better polyp detection rate were older age (P < 0.001), no history of previous abdominal surgery (P = 0.04), patients not having esophagogastroduodenoscopy in the same setting (P = 0.003), trainee-performed procedures (P = 0.01), usage of hyoscine (P = 0.01) and procedures performed for polyp follow-up (P = 0.01). The limitations of the study were that it was a single-center experience, no blinding was possible, and there were a large number of endoscopists.

    CONCLUSION: CAC did not significantly different from SC in term of cecal intubation time and polyp detection rate.

    Matched MeSH terms: Scopolamine Hydrobromide/therapeutic use
  12. Chidambaram SB, Pandian A, Sekar S, Haridass S, Vijayan R, Thiyagarajan LK, et al.
    Environ Toxicol, 2016 Dec;31(12):1955-1963.
    PMID: 26434561 DOI: 10.1002/tox.22196
    PURPOSE: Present study was undertaken to evaluate the antiamnesic effect of Sesamum indicum (S. indicum) seeds (standardized for sesamin, a lignan, content) in scopolamine, a muscarinic antagonist intoxicated mice.

    METHODS: Male Swiss albino mice (18-22 g bw) were pretreated with methanolic extract of sesame seeds (MSSE) (100 and 200 mg/kg/day, p.o) for a period of 14 days. Scopolamine (0.3 mg/kg, i.p.) was injected on day 14, 45 ± 10 min after MSSE administration. Antiamnesic effect of MSSE was evaluated using step-down latency (SDL) on passive avoidance apparatus and transfer latency (TL) on an elevated plus maze. To unravel the mechanism of action, we examined the effects of MSSE on the genes such as acetyl cholinesterase (AChE), muscarinic receptor M1 subtype (mAChRM1 ), and brain derived neurotrophic factor (BDNF) expression within hippocampus of experimental mice. Further, its effects on bax and bcl-2 were also evaluated. Histopathological examination of hippocampal CA1 region was performed using cresyl violet staining.

    RESULTS: MSSE treatment produced a significant and dose dependent increase in step down latency in passive avoidance test and decrease in transfer latency in elevated plus maze in scopolamine intoxicated injected mice. MSSE down-regulated AChE and mAChRM1 and up-regulated BDNF mRNA expression. Further, it significantly down-regulated the bax and caspase 3 and up-regulated bcl-2 expression in scopolamine intoxicated mice brains. Mice treated with MSSE showed increased neuronal counts in hippocampal CA1 region when compared with scopolamine-vehicle treated mice.

    CONCLUSION: Sesame seeds have the ability to interact with cholinergic components involved in memory function/restoration and also an interesting candidate to be considered for future cognitive research. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1955-1963, 2016.

    Matched MeSH terms: Scopolamine Hydrobromide/toxicity*
  13. Azmi N, Norman C, Spicer CH, Bennett GW
    Behav Pharmacol, 2006 Jun;17(4):357-62.
    PMID: 16914954
    Various lines of evidence suggest a role in cognition for the endogenous neuropeptide, neurotensin, involving an interaction with the central nervous system cholinergic pathways. A preliminary study has shown that central administration of neurotensin enhances spatial and nonspatial working memory in the presence of scopolamine, a muscarinic receptor antagonist which induces memory deficits. Utilizing similar methods, the present study employed a two-trial novel object discrimination task to determine the acute effect of a neurotensin peptide analogue with improved metabolic stability, PD149163, on recognition memory in Lister hooded rats. Consistent with previous findings with neurotensin, animals receiving an intracerebroventricular injection of PD149163 (3 microg) significantly discriminated the novel from familiar object during the choice trial. In addition, a similar dose of PD149163 restored the scopolamine-induced deficit in novelty recognition. The restoration effect on scopolamine-induced amnesia produced by PD149163 was blocked by SR142948A, a nonselective neurotensin receptor antagonist, at a dose of 1 mg/kg (intraperitonial) but not at 0.1 mg/kg. In conclusion, the present results confirm a role for neurotensin in mediating memory processes, possibly via central cholinergic mechanisms.
    Matched MeSH terms: Scopolamine Hydrobromide/pharmacology*
  14. Retinasamy T, Shaikh MF, Kumari Y, Othman I
    Front Pharmacol, 2019;10:1216.
    PMID: 31736744 DOI: 10.3389/fphar.2019.01216
    Alzheimer's disease (AD) is a chronic neurodegenerative brain disease which is characterized by impairment in cognitive functioning. Orthosiphon stamineus (OS) Benth. (Lamiaceae) is a medicinal plant found around Southeast Asia that has been employed as treatments for various diseases. OS extract contains many active compounds that have been shown to possess various pharmacological properties whereby in vitro studies have demonstrated neuroprotective as well as cholinesterase inhibitory effects. This study, therefore aimed at determining whether this Malaysian plant derived flavonoid can reverse scopolamine induced learning and memory dysfunction in the novel object recognition (NOR) test and the elevated plus maze (EPM) test. In the present study, rats were treated once daily with OS 50 mg/kg, 100 mg/kg, 200 mg/kg and donepezil 1 mg/kg via oral dosing and were given intraperitoneal (ip) injection of scopolamine 1 mg/kg daily to induce cognitive deficits. Rats were subjected to behavioral analysis to assess learning and memory functions and hippocampal tissues were extracted for gene expression and immunohistochemistry studies. All the three doses demonstrated improved scopolamine-induced impairment by showing shortened transfer latency as well as the higher inflexion ratio when compared to the negative control group. OS extract also exhibited memory-enhancing activity against chronic scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by an increase in the recognition index. OS extract was observed to have modulated the mRNA expression of CREB1, BDNF, and TRKB genes and pretreatment with OS extract were observed to have increased the immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by the DCX-positive stained cells. These research findings suggest that the OS ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.
    Matched MeSH terms: Scopolamine Hydrobromide
  15. Nasir MN, Abdullah J, Habsah M, Ghani RI, Rammes G
    Phytomedicine, 2012 Feb 15;19(3-4):311-6.
    PMID: 22112723 DOI: 10.1016/j.phymed.2011.10.004
    The asiatic acid, a triterpenoids isolated from Centella asiatica was used to delineate its inhibitory effect on acetylcholinesterase (AChE) properties, excitatory post synaptic potential (EPSP) and locomotor activity. This study is consistent with asiatic acid having an effect on AChE, a selective GABA(B) receptor agonist and no sedative effect on locomotor.
    Matched MeSH terms: Scopolamine Hydrobromide/pharmacology
  16. George A, Ng CP, O'Callaghan M, Jensen GS, Wong HJ
    PMID: 24886679 DOI: 10.1186/1472-6882-14-161
    Polygonum minus Huds.is a culinary flavouring that is common in South East Asian cuisine and as a remedy for diverse maladies ranging from indigestion to poor eyesight. The leaves of this herb have been reported to be high in antioxidants. Flavonoids which have been associated with memory, cognition and protection against neurodegeneration were found in P. minus.
    Matched MeSH terms: Scopolamine Hydrobromide
  17. Mani V, Parle M, Ramasamy K, Abdul Majeed AB
    J Sci Food Agric, 2011 Jan 15;91(1):186-92.
    PMID: 20848667 DOI: 10.1002/jsfa.4171
    Coriandrum sativum L., commonly known as coriander and belonging to the family Apiaceae (Umbelliferae), is cultivated throughout the world for its nutritional value. The present study was undertaken to investigate the effects of fresh Coriandrum sativum leaves (CSL) on cognitive functions, total serum cholesterol levels and brain cholinesterase activity in mice. In this study, CSL (5, 10 and 15% w/w of diet) was fed orally with a specially prepared diet for 45 days consecutively to experimental animals. Elevated plus-maze and passive avoidance apparatus served as the exteroceptive behavioral models for testing memory. Diazepam, scopolamine and ageing-induced amnesia served as the interoceptive behavioral models.
    Matched MeSH terms: Scopolamine Hydrobromide
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