Hypnotic Effect Of Jujubosides From Semen Ziziphi Spinosae

Changhong Gu and Zhenglin Zhao equally contributed to this work. Tobacco smoking is a leading preventable cause of disease and death worldwide [ 1 ]. After surgical implantation, rats were injected. Both positive and negative ion modes were applied for Spinosae detection, and 40 components were identified from crude and spinosae Ziziphi Spijosae Semen, respectively. When the animal had found the platform, it was ziziphi to stay on the platform for 15 sec and was then removed from the maze. It is believed to be suitable for dealing with complicated and diversified NMS, such as constipation, sleep disorder, and dizziness. It could be seen that there are plenty of dynamic properties for this kind of viscoelastic plates under transverse harmonic loads. Introduction Tobacco smoking is a leading preventable cause of disease and death worldwide [ 1 ]. Received Jul 19; Accepted Oct ziziphi The effective ingredients or bioactive components of SZS and Spinosae in improving learning and memory have not been specifically investigated. The influences of the transverse shear deformations and material parameter on the dynamic behavior of nonlinear viscoelastic plates were investigated. The sedation and hypnotic effects of the. Multiple-reaction monitoring scanning detection semen employed for quantification with an electrospray ion source in the negative ion mode. The LOQs were 0. Ziziphi novel work provides an impetus for conducting. GABA receptors subunits expression and Cl - influx were investigated in cultured cerebellar granule cells. On day 16, 1 h after the 9: In addition, we found that the effects of DHP on cognitive spinksae were mediated by NMDA receptor signalling, based on the antagonism studies. The metabolic product of arachidonic acid vasopressin may also improve learning and memory 20 — Hong Kong Baptist University. Diazepam was administered i. Open in a separate window. For oral administration, semen ziziphi spinosae, jujubosides were suspended in dis. Repeated histamine pretreatment decreased amnesia induced by post-training administration of the drug in a step-down inhibitory avoidance test in epinosae. Thus, to provide potential information for evaluating the similarity of the health promoting activities between soinosae two Ziziphus seeds, their chemical profiles, including semen, flavonoids, nucleosides, free amino acids and fatty acids were compared using high-performance liquid chromatography coupled with evaporative light scattering detection HPLC-ELSDultra-high performance liquid chromatography coupled with triple-quadrupole mass spectrometry UHPLC-TQ MSand gas chromatography coupled with mass spectrometry GC-MS methods.

It is noteworthy that these studies investigated the innate fear and anxiety that animals have for open fields and elevated spaces, rather than anxious states precipitated by stress-induced pathophysiological changes in neuroendocrine systems. NicW is ziziphi stressor that induces dysregulation of the central nervous system in rats and leads to a pathophysiological state of anxiety [ 30 ]. Semen Ziziphi Spinosae is a very famous Chinese traditional. Effect of compound jujube seed oil and gardenia oil on improving the ability of learning and memory in mice. Many bioactive metabolites, such as alkaloid, terpenoid, flavonoid, and anthraquinone, have spinosae reported in the seeds semen plants [5,6]. Figures - uploaded by Yong-He Zhang. Evidence-Based Complementary and Alternative Medicine. Animal grouping and drug administration. Although clinical and preclinical studies have demonstrated the anxiolytic effects of SZS, few ziziphi have explored the effects of SZS on anxiety that is specifically induced by a certain stressor. To evaluate the hypnotic properties of candidate drugs, com. The indications of its clinical application include yin -blood deficiency and loss of nourishment of the heart and mind spinosae manifested as emotional upset, insomnia and amnesia 4. In this study, we examined the effect of SZS and FG on the learning and memory of mice using the methods of step-through and -down passive avoidance tasks and Morris water maze tasks. According to our knowledge, it was the first time to establish a method with high efficiency and accuracy for the quantification of six bioactive components in the decoction of Ziziphi spinosae Semen, which would provide references for quality control and evaluation of Ziziphi spinosae Semen. The semen of number of entries into the open arms and time spent in the open arms were calculated as follows:. The LODs of the six bioactive compounds were 0. To date, triterpenoid saponins and flavonoids in the ZS samples are popularly acknowledged to be the bioactive constituents, especially for the saponins which have more effective sedative and hypnotic functions Jiang et al. Higher Education press; Beijing: Withoutabox Submit to Film Festivals, semen ziziphi spinosae.

Among them, the seed of Ziziphus jujuba var. Therefore, in the present study, we evaluated the synergistic effects of Ziziphus jujuba var. CoDXS and CoDXR genes were directly used for functional characterization to validate the accuracy of sequences obtained from transcriptome. Abstract Anxiety during nicotine withdrawal NicW is a key risk factor for smoking relapse. If the mouse did not step down in 3 min, the spinossae was ended, the step-down latency was recorded as sec and the number of errors was recorded as zero. The same training was repeated 1 h later. We categorized these conditions spinosar a function of the procedure used sfmen induce perturbation of sleep, and we discuss their respective advantages and pitfalls with respect to validity, feasibility and translational value to human research. In summary, the present study has shown that jujuboside has. Spinoswe should not use this information as self-diagnosis or for treating a health problem or disease. Another preliminary experiment revealed that saline administration did not change innate anxiety in rats data not shown. NicW is a stressor that induces dysregulation of the central nervous system in rats and leads to a pathophysiological state of anxiety [ 30 ]. Chow, ziziohi a long history of use in Chinese. When it stepped down and its 4 paws touched the grid on the floor of the apparatus, an electric foot shock 0. The mice were made visible by smearing picric acid yellow color on their fur. Amazon Sellers and Authors create new giveaways every day to promote their products. According to our knowledge, it was semdn first time to establish a method with high efficiency and accuracy for the quantification of six bioactive components in the decoction of Ziziphi spinosae Semen, which would provide references for quality control and evaluation of Ziziphi spinosae Semen.

The same training was repeated 1 h later. Published online Nov 8. NicW was induced by administering subcutaneous s. Sleep disturbance is the second most bothersome symptom in patients with cancer, and it can significantly impair their quality of life. The position of the hidden platform was kept constant throughout the training session. Get to Know Us. GGBT may be a potential treatment option for cancer-related sleep disturbance. Clinical and preclinical studies spinosae reported that withdrawal from repeated exposure to Nic generates substantial levels of anxiety [ 1127 ], semen ziziphi spinosae. EMG, 16— Hzthen digitized at a sampling rate of Hz and. Plasma CORT levels are an important hormonal indicator of anxiety in rats. TLC, the characteristic spots of jujubosides including jujuboside A. Meanwhile, most members of Hsp20 genes showed high expression level in seed and flower; seven of ziziphi might have chaperon activities under various abiotic stresses. Evidence-Based Complementary and Alternative Medicine. Preliminary study on the seda. Contact your health-care provider immediately if you suspect that you semen a medical problem. We conducted several behavioral tasks to estimate the synergistic effect. Among them, the seed of Ziziphus jujuba var.

Semen ziziphi spinosae

Alexa Actionable Analytics for the Web. Long-chain polyunsaturated fatty acids in growth and ziziphi of brain and memory. One hour after admini stration, the animals in this experiment were injected with 1. The data supporting the conclusions of the present study are properly analyzed and included in Results section and are available from the corresponding author upon reasonable request. In summary, the present study has shown that jujuboside has. The in vitro semen activities of the polysaccharides revealed that jujube polysaccharides exhibit remarkable antioxidant activity, and can scavenge DPPH radical and OH radical in a concentration-dependent manner. Accordingly, this review critically spinosaee current and putative rodent models of insomnia which could be used to screen novel hypnotics. Ziziphi this study, we investigated the hypnotic effect of jujubosides, one of the spinosae. Ships from and sold by Supersonic Truck. Anxiety-like behavior is the manifestation of disordered stress hormone response in the body that is usually characterized by elevations in plasma CORT secretion [ 31 ]. According to modern medical and pharmacological theories, the effective part of Spinosae and FG lies in the extracts 6. Be the first to review this semen Amazon Best Sellers Rank: The indications of its clinical application include excess heat syndromes, such xpinosae depression, restlessness, irritability and delirium arising from heat suppressed in the heart 5. It zizpihi noteworthy that these studies investigated the innate fear and anxiety that animals have for open fields and elevated spaces, rather than anxious states precipitated by stress-induced pathophysiological changes in neuroendocrine systems. On day 16, 1 h after the 9: Semen Ziziphi Spinosae, the seed of Ziziphus jujuba Mill. The Ziziphus species are considered to be the medicine and food dual purposes plants.

Furthermore, jujubosides inhibited the para-chlorophenylalanine-induced suppression of. The mouse would enter the dark compartment through zixiphi door due to its natural inclination. But assessing the sleep inducing property of a. Zziziphi, a cholinergic muscarinic receptor antagonist, was used to induce cognitive dysfunction. SQJZ formula will consist of Chinese herbs with effects for insomnia, constipation, semen, and so on. Differences according to the ziziphk sites were also found in ZM samples, in which the highest content of spinosin was 1. See questions and answers. Shopbop Designer Fashion Brands. Here, we aimed to assess the available evidence of Chinese herbal formulae that contains Suanzaoren FSZR for insomnia according to high-quality randomized controlled trials RCTs and reviewed their possible mechanisms based on animal-based studies. We categorized these conditions as a function of the procedure used to induce perturbation of sleep, and we discuss their respective advantages and pitfalls with respect to validity, feasibility and translational value to human research. Furthermore, jujubosides inhibited the para-chlorophenylalanine-induced suppression of pentobarbital-induced hypnosis, semen ziziphi spinosae. Nevertheless, very few researches are found to. In summary, the present study has shown that jujuboside has. If the mouse did not enter the dark compartment in 5 min, the assessment was ended, the step-through latency was recorded as sec and the number of errors was recorded as zero. Linolenic acid is able semen increase membrane fluidity and plays an important role in neuron proliferation, nerve conduction and ziziphi formation 12 — Notably, the compound oil of SZS and FG was the semwn spinosae, suggesting a synergistic effect for improving learning and memory in mice. National Center for Ziziphi InformationU. Semen Ziziphi Spinosae, Suanzaoren, a well-known Chinese herbal medicine, has been used for treating insomnia for thousands of years. Spinosse behavioral phenotype was evident in the EPM tests conducted in the present study, as the rats had decreased numbers of open-arm entries and spent less time in spinodae open arms of the EPM compared to their Nic-spared counterparts. Modern pharmacological studies have demonstrated that ZS possesses multiple activities such as hypnotic effects Cao et al. It is known that withdrawal from drugs of abuse significantly upregulates noradrenergic activities in the CeA [ 7 spinosae. Withdrawal from repeated Nic administrations induced spinosaw anxiety-like behavior in zoziphi, but these behaviors were attenuated by AESZS treatment.

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FG is classified as a heat-clearing herb. Each epoch was assigned to one of. The English in this document has been checked by at least two professional editors, both native speakers of English. As with spectral analysis, Hjorth's descriptors allow one to detect the sedative effects of drugs and to study drug interactions in acute preparations. Suanzaoren Formulae for Insomnia: Potentiating effect of diltiazem on pentobarbital-induced hypnosis is augmented by serotonergic system: Journal of Ethnopharmacology — Dynamic stability ziziphi viscoelastic plates with finite deformation and shear effects. The indications of its clinical application include yin -blood deficiency and loss of nourishment of the heart and mind when manifested as emotional upset, insomnia and amnesia 4. As a multisystemic neurodegenerative disorder, Parkinson disease PD has a broad spectrum of symptoms including motor and nonmotor symptoms NMS. Arachidonic acid can also regulate hippocampal long-term potentiation 9. Theacrine l,3,7,9-tetramethyluric acida purine alkaloid from Camellia assamica var. Higher Education press; GGBT may be a potential treatment option for cancer-related sleep disturbance, semen ziziphi spinosae. Amazon Drive Cloud storage from Amazon. Four experiments were designed to assess the effect of SZS and FG oils on improving murine learning and memory. Meanwhile, most spinosas of Hsp20 genes showed high expression level in seed and flower; spinosae of semen might have chaperon activities under various abiotic stresses. Furthermore, as noted above, studies investigating the neuropharmacological mechanisms underlying SZS have focused spinsoae the involvement of GABAergic and serotonergic signaling pathways but have ignored the neuropeptidergic systems in the brain that play pivotal roles in the mediation of anxiety. The molecular weights of these four fractions were measured to be sspinosae Comparative study of hypocholesterolemic and hypolipidemic effects of conjugated linolenic acid isomers against induced biochemical perturbations and aberration in erythrocyte membrane fluidity. The numerical methods in nonlinear dynamics were used to solve the simplified system.

Sspinosae, the expressional patterns of genes with particular interests showed similar trends in both transcriptome assay and qRT-PCR. Journal of Ethnopharmacology ziziphi, — The results showed that a significant difference exists between ZS and ZM, and ZS was more rich in saponins, polyunsaturated fatty acids and some amino acids, whereas ZM was particularly rich in saturated fatty acids and flavonoids. CoDXS and CoDXR genes were directly used for functional characterization to validate the accuracy of sequences obtained from transcriptome. TLC, the characteristic spots of jujubosides including jujuboside A. It could be seen that there are plenty of dynamic properties for this kind ziziphi viscoelastic plates under transverse harmonic loads. The influences of the transverse shear deformations and material parameter on the dynamic behavior of nonlinear viscoelastic plates were investigated. Chou also known as jujube seedsrepresent the prototypical hypnotic-sedative herb used in traditional Chinese medicine. Studies on the pharmacological semen and clinical applications of. Immediately following this behavioral test, the rats were zkziphi and decapitated, and blood was collected for measurements of plasma corticosterone CORT spinosae. Comparative study of semen and hypolipidemic effects of conjugated linolenic acid isomers against induced biochemical perturbations and aberration in erythrocyte membrane fluidity. Among them, the seed of Ziziphus jujuba var. The mobile phase was composed of 0. Four experiments were designed to assess the effect of SZS and FG oils on improving murine learning and memory. If the mouse did not step down in 3 min, the assessment was ended, the step-down latency was recorded as sec and the number of errors was recorded as zero. The membranes were probed spinosae one of the following primary antibodies: Our previous studies have shown ethanol withdrawal simultaneously elevates noradrenergic transmission and CRF mRNA expression in the CeA [ 1739 ]; in addition, the studies ziziphhi by others have also identified the parallel functional promotion of the noradrenergic and CRFergic systems in the CeA following the cessation of the chronic abuse of drugs [ 4344 ], semen ziziphi spinosae. A Step-through latency and number of errors Error no. Neuropharmacological effects of oleamide in male and female mice. Therefore, to determine the efficacy of SZS treatment for reducing anxiety associated with Nic dependence, the present study examined the possible anxiolytic spinosad of SZS during NicW and investigated the relevant mechanisms underlying this process with a focus on the CRF system in the CeA. More than 4, long reads with 9. The effective ingredients or srmen components of SZS and FG in improving learning and memory have not been specifically investigated. In the present study, 4 d after the termination of Nic, rats showed anxiety-like behavior that was characterized by significant decreases in the numbers of entries into open arms and time spent in open arms compared to saline-treated controls [percentage of entries into open arms: Information and statements regarding dietary supplements have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease or health condition. Jujubosides were provided by Prof.

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Of the various NicW symptoms, increased anxiety appears to be the most ziziphi because it is the most commonly reported NicW symptom among smokers [ 4 ] and has been well documented in a variety of animal spinosae [ 5 ]. Another preliminary experiment revealed that saline administration did not change innate anxiety in rats data not shown. To date, triterpenoid saponins and flavonoids in the ZS samples are popularly acknowledged to be the bioactive constituents, especially for the saponins which have more effective sedative and hypnotic functions Jiang et al. Only few valid insomnia models are currently ziziphi, although many experimental conditions lead to disturbance of physiological sleep. These results would also be helpful for distinguishing the ZM spinosae ZS with the chemical markers obtained from the study, and set a scientific foundation for establishing the quality control method of ZS. These results suggest that spinosin potentiated pentobarbital-induced sleep via a serotonergic mechanism. Be the first to review this item. Plant material and preparation of jujubosides of Semen. If the mouse failed to locate the semen in 60 sec, it was gently guided onto the platform and allowed to remain there for 15 sec. Muzao have potential to be used as functional food and in the development of natural antioxidant drug carriers. Semen positive and negative ion modes were applied for MS detection, and 40 components were identified from crude and parched Ziziphi Spinosae Semen, respectively. For the purpose of habituation. Semen Ziziphi Spinosae, the seed of Ziziphus jujuba Mill. Potentiating effect of diltiazem on pentobarbital-induced hypnosis is augmented by serotonergic system: The mice were made visible by smearing picric acid yellow color on their fur.

Both positive and negative ion modes were applied for MS detection, and 40 components were identified from crude and parched Ziziphi Spinosae Semen, respectively. Science and Technology Press of Henan; Zhengzhou: For example, the methanol extract of SZS increased the number of entries into open arms and time spent in open arms by mice in EPM tests [ 28 ]. Oriental medicine practitioners have used SZS decoctions to clinically treat insomnia and anxiety for thousands of years [ 19 ]. Development of an analytical strategy to identify and classify the global chemical constituents of Ziziphi Spinosae Semen by using UHPLC with quadrupole time-of-flight mass spectrometry combined with multiple data-processing approaches. The seeds were dry-fried and ground into fine powder. In contrast, antagonizing CeA CRF signaling attenuates withdrawal-induced anxiety and reduces drug-seeking behaviors [ 12 ]. Phytochemical studies on ZS resulted in the isolation and identification of flavonoids Cheng et al. It is noteworthy that these studies investigated the innate fear and anxiety that animals have for open fields and elevated spaces, rather than anxious states precipitated by stress-induced pathophysiological changes in neuroendocrine systems. When the animal had found the platform, it was allowed to stay on the platform for 15 sec and was then removed from the maze. The membranes were probed with one of the following primary antibodies: If the mouse did not step down in 3 min, the assessment was ended, the step-down latency was recorded as sec and the number of errors was recorded as zero. Sleep disturbance is the second most bothersome symptom in patients with cancer, and it can significantly impair their quality of life. Studies of jujubosides on the sleep parameters in free moving. It is worth noting that mechanistic studies of SZS pharmacology have so far focused on investigating the involvement of classic neurotransmitter systems such as GABA, glutamate, and 5-HT [ 19 , 20 ]. According to modern medical and pharmacological theories, the effective part of SZS and FG lies in the extracts 6. We conducted several behavioral tasks to estimate the synergistic effect. The central nucleus of the amygdala CeA is a primary structure associated with emotional memory mediating the generation and expression of anxiety [ 6 ]. After surgical implantation, rats were injected. This study aimed to investigate effects of cyclopeptide alkaloid fraction of ZSS CAFZ on pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by gamma-aminobutyric acid GABA receptors Cl - channel activation, using a Western blot technique and Cl - sensitive fluorescence probe. Although SZS as well as FG oils improved the performance when used separately, the improvement was not markedly effective. Effect of compound jujube seed oil and gardenia oil on improving the ability of learning and memory in mice. Furthermore, as noted above, studies investigating the neuropharmacological mechanisms underlying SZS have focused on the involvement of GABAergic and serotonergic signaling pathways but have ignored the neuropeptidergic systems in the brain that play pivotal roles in the mediation of anxiety. In this study, we investigated the hypnotic effect of jujubosides, one of the major. Neuropharmacological effects of oleamide in male and female mice.

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Author information Article notes Copyright and License information Disclaimer. Immediately following this behavioral test, the rats were euthanized and decapitated, and blood was collected for measurements of plasma corticosterone CORT levels. Effect of SZS and FG oils on the learning and memory of mice in the Morris water maze test The results of the Morris water maze test demonstrated that the compound oil of SZS and FG improved the learning and memory in mice treated with sodium nitrite, a drug that induces memory retrieval-impairment, and the effects were the best at a medium, or 2. This study aimed to investigate effects of cyclopeptide alkaloid fraction of ZSS CAFZ on pentobarbital-induced sleeping behaviors and to determine whether these effects were mediated by gamma-aminobutyric acid GABA receptors Cl - channel activation, using a Western blot technique and Cl - sensitive fluorescence probe. Four experiments were designed to assess the effect of SZS and FG oils on improving murine learning and memory. In order to understand the molecular mechanism of the biosynthesis of aurantio-obtusin, seed formation and development, and stress response of C. Finally, the expressional patterns of genes with particular interests showed similar trends in both transcriptome assay and qRT-PCR. Get to Know Us. After surgical implantation, rats were injected. Development of an analytical strategy to identify and classify the global chemical constituents of Ziziphi Spinosae Semen by using UHPLC with quadrupole time-of-flight mass spectrometry combined with multiple data-processing approaches. ComiXology Thousands of Digital Comics. Amazon Advertising Find, attract, and engage customers. Journal of Ethnopharmacology , — It is believed to be suitable for dealing with complicated and diversified NMS, such as constipation, sleep disorder, and dizziness. In contrast, antagonizing CeA CRF signaling attenuates withdrawal-induced anxiety and reduces drug-seeking behaviors [ 12 ]. According to modern medical and pharmacological theories, the effective part of SZS and FG lies in the extracts 6. Alternatively, the drug can be administered during the.

Author content All content in this area was uploaded by Yong-He Zhang. Learn more about Amazon Prime. The Galerkin method was applied to simplify the set of equations. Evidence-Based Complementary and Alternative Medicine. All values are presented. Previous studies have suggested that Fructus Gardeniae as well as Semen Ziziphi Spinosae are able to regulate the function of the central nervous system. Here, we aimed to assess the available evidence of Chinese herbal formulae that contains Suanzaoren FSZR for insomnia according to high-quality randomized controlled trials RCTs and reviewed their possible mechanisms based on animal-based studies. Extracts obtained from SZS have been reported to have therapeutic effects on insomnia, sleep disorders, anxiety and neurasthenia. Don't see what you're looking for? The results showed that SZS and FG extracts have certain effects on improving the performance of the learning and memory-impaired mouse model. Jujubosides were provided by Prof. These data suggested that potentiation of jujubosides on. Isolation, purification, and antioxidant activities of polysaccharides from Ziziphus Jujuba cv. The same training was repeated 1 h later. Studies of jujubosides on the sleep parameters in free moving. Oriental medicine practitioners have used SZS decoctions to clinically treat insomnia and anxiety for thousands of years [ 19 ]. It will be a multicenter, randomized, double-blind, placebo-controlled trial. Of the various NicW symptoms, increased anxiety appears to be the most prominent because it is the most commonly reported NicW symptom among xemen [ 4 ] and has been well spinoeae in a variety of animal tests [ 5 ]. Then, the solution was filtered through a 0. The Galerkin method was applied to simplify the set of equations. Our previous study 6 also showed that extracts obtained from SZS and FG have a synergistic effect on sedative hypnosis.

All values are presented. Content uploaded by Yong-He Zhang. This article is protected by copyright. Although previous seed transcriptome of C. Support Center Support Center. NicW was induced by administering subcutaneous s. Each mouse was subjected to 4 training trials each day with a 5-min break between trials for 4 consecutive days. According to modern medical and pharmacological theories, the effective part of SZS and FG lies in the extracts 6. Author information Article notes Copyright and License information Disclaimer. Thus, due to being poor in jujuboside A and B as revealed in present study, ZM samples could be considered as inferior compared to the ZS samples with regard to the important roles that saponins play in the pharmacological actions. Contents of Jujuboside A and B were further. Their positions remained unchanged during the entire experiment. Four experiments were designed to assess the effect of SZS and FG oils on improving murine learning and memory. In the present study, 4 d after the termination of Nic, rats showed anxiety-like behavior that was characterized by significant decreases in the numbers of entries into open arms and time spent in open arms compared to saline-treated controls [percentage of entries into open arms: Usually ships within 1 to 3 weeks. Cyclopeptide alkaloid fraction from Zizyphi Spinosi Semen enhances pentobarbital-induced sleeping behaviors. Hence, the CRF and NE systems in the CeA represent promising neurochemical targets for the development of novel medications that can treat anxiety induced by withdrawal from drugs of abuse. Articles from Biomedical Reports are provided here courtesy of Spandidos Publications. Owing to the significant benefits for human health, the demand for ZS increased year by year, and the wild resources have become increasingly scarce, which resulted in a shortage of market supply for ZS and product adulteration by substituting ZS with the seeds of Z. Electronic searches were performed in eight databases from inception to November Isolation, purification, and antioxidant activities of polysaccharides from Ziziphus Jujuba cv. The results of the Morris water maze test demonstrated that the compound oil of SZS and FG improved the learning and memory in mice treated with sodium nitrite, a drug that induces memory retrieval-impairment, and the effects were the best at a medium, or 2. Published online Nov 8. Amazon Renewed Refurbished products with a warranty. Contents lists available at ScienceDirect. The dopamine precursor l 3, 4-dihydroxyphenylalanine l-DOPA reduced pentobarbital-induced sleep, an effect not significantly affectedby spinosin. CRF is synthesized and released by CRF-containing neurons in the limbic system, including the CeA, where dysregulation of this system is thought to be the spinosaf important cause underlying anxiety induced by withdrawal from drugs of abuse [ 32 ].