Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways (original) (raw)
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Anxiolytic-like effect of the leaves of Pseudospondias microcarpa (A. Rich.) Engl. in mice
Journal of Basic and Clinical Physiology and Pharmacology, 2016
Background: Pseudospondias microcarpa is a plant used for managing various diseases including CNS disorders. Previous studies showed sedative and anticonvulsant effects, suggesting possible anxiolytic activity. This study therefore assessed the anxiolytic effects of P. microcarpa hydroethanolic leaf extract (PME) in mice. Methods: In the present study, anxiolytic-like effect of the extract in behavioural paradigms of anxiety-the elevated plus maze (EPM), light/dark box (LDB), social interaction test and stress-induced hyperthermia (SIH)-was evaluated. Results: Mice treated with PME (30-300 mg kg −1 , p.o.) exhibited anxiolytic-like activity similar to diazepam in all the anxiety models used. The extract increased open arm activity (p < 0.05) in the EPM as well as increasing the time spent in the lit area in relation to the time spent in the dark area of the LDB. Sociability and preference for social novelty significantly (p < 0.05-0.001) increased in mice treated with PME. In the SIH paradigm in mice, both PME and the benzodiazepine receptor agonist, diazepam, significantly (p < 0.05) reduced the stressinduced increase in rectal temperature. The extract did not impair motor coordination and balance in the beam walk test. Conclusions: Results of the present study indicate that PME possesses anxiolytic-like effects in mice.
Journal of Ethnopharmacology, 2017
Ethnopharmacological relevance: Maerua angolensis DC (Capparaceae) has been employed in the management of several central nervous system (CNS) disorders including anxiety. This study evaluated the anxiolytic effects of the petroleum ether/ethyl acetate fraction stem bark extract and its possible mechanism(s) using zebrafish anxiety models. Methods: Adult zebrafish, tested in the novel tank and light dark tests, have shown by previous authors to be sensitive to the anxiolytic effects of known anxiolytic drugs. Adult zebrafish were treated with M. angolensis extract, fluoxetine, desipramine, and diazepam followed by testing in the novel tank and light dark tests. We further assessed the effect of the extract on anxiety after inducing an anxiogenic phenotype using the ethanolwithdrawal and chronic unpredictable stress (CUS) tests. The anxiolytic effect was further investigated after pretreatment with flumazenil, granisetron, cyproheptadine, methysergide and pizotifen. Results: M. angolensis extract, similar to fluoxetine and desipramine, demonstrated significant anxiolytic behaviour at doses that did not reduce locomotor activity significantly. Similar anxiolytic effects were recorded in the ethanol withdrawal-induced anxiety test. Furthermore, the anxiogenic effects induced by the CUS paradigm were significantly reversed by treatment M. angolensis extract and fluoxetine. The anxiolytic effects of M. angolensis extract were however reversed after pre-treatment with flumazenil, granisetron, cyproheptadine, methysergide and pizotifen. Conclusions: Taken together, this suggests that the petroleum ether/ ethyl acetate fraction of M. angolensis possesses significant anxiolytic activity, which could partly be accounted for by an interaction with the serotoninergic system and the GABA A receptor.
Pharmacy & Pharmacology International Journal, 2020
Anxiety disorders are among the top ten diseases responsible for disability worldwide, and Brazil, in 2015, was considered by the World Health Organization (WHO) the country with the highest rate of anxiety disorders in the world, with 9.3% of the population. 1 Abstinence-induced anxiety is a common problem in drug abuse. 2 This problem is associated when consumption is discontinued or abruptly reduced, with the occurrence of symptoms such as trembling, anxiety, insomnia, agitation, hypervigilance, irritability, piloerection and, sometimes, seizures. 3 Benzodiazepines (GABA receptor agonists) and selective serotonin reuptake inhibitors (SSRIs) are the drugs of choice for the treatment of anxiety. 2 SSRIs are also commonly used to treat depressive disorders. 4 However, the chronic use of benzodiazepines causes tolerance, and abrupt treatment discontinuation may lead to withdrawal syndrome. 5 On the other hand, the chronic use of SSRIs can result in considerable side effects, 6 therefore the search for new compounds with anxiolytic and antidepressant properties that cause fewer adverse effects continues. 7 Animal models are used for the assessment of new anxiolytic drugs. These pre-clinical models and screening tests support the studies, since clinical trials are expensive, 8 especially regarding the central nervous system therapy. 9 Currently, the zebrafish (Danio rerio) has been used in behavioral neuroscience, including research involving the brain and psychopharmacology. 9 This vertebrate animal is considered a significant model in preclinical studies, because its genotype has 70% homology with mammalian neurotransmitter receptors. 10 Because of the side effects associated with allopathic drugs, there is a growing interest in the development of alternative therapies to treat psychiatric disorders. 11 Previous studies have demonstrated the anxiolytic action of several phytochemical groups, such as polyphenols and flavonoids found in plants. 12 In this context, Azadirachta indica A. Juss. (Neem), which belongs to the Meliaceae family, native to India, and also found in Brazil, is rich in flavonoids. 13 Both the bark and leaves of A. indica contain biologically active molecules, which have hypolipidemic, hypoglycemic, immunostimulatory, hepatoprotective,
PLOS ONE
Introduction Pseudospondias microcarpa (Anacardiaceae) is a plant widely used traditionally for treating various central nervous system disorders. A previous study in our laboratory confirmed that the hydroethanolic leaf extract (PME) of the plant produces an antidepressant-like effect in rodent models of behavioral despair. However, its effect on depressive-like behavior induced by chronic mild stress (CMS) and its time course of action are still unknown. In this context, the long-term effects of PME on cognitive function and depressive- and anxiety-like behavior caused by CMS were assessed. Methods Male ICR mice were exposed to CMS for nine weeks and anhedonia was evaluated by monitoring sucrose intake (SIT) weekly. PME (30, 100, or 300 mg kg-1) or fluoxetine (FLX) (3, 10, or 30 mg kg-1) was administered to the mice during the last six weeks of CMS. Behavioral tests—coat state, splash test, forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM), open fiel...
Zebrafish as a Useful Tool in the Research of Natural Products With Potential Anxiolytic Effects
Frontiers in Behavioral Neuroscience, 2022
Zebrafish (Danio rerio) is a popular and valuable species used in many different biomedical research areas. The complex behavior that fish exhibit in response to different stimuli allows researchers to explore the biological and pharmacological basis of affective and mood disorders. In this sense, anxiety is commonly studied in preclinical research with animal models in rodents. During the last decade, those models have been successfully adapted to zebrafish. Stressful stimuli, such as novel environments, chemical substances, light conditions, and predator images, can trigger defensive behaviors considered indicators of an anxiety-like state. In the first stage, models were adapted and validated with different stressors and anxiolytic drugs with promising results and are now successfully used to generate scientific knowledge. In that sense, zebrafish allows several routes of administration and other methodological advantages to explore the anxiolytic effects of natural products in b...
Zebrafish
Anxiety disorders appear to involve distinct neurobiological mechanisms and several medications are available against this mental health problem. However, pharmacological therapeutic approaches display undesirable side effects for patients, particularly when long-term therapy is required. Some evidences have suggested that Coriandrum sativum extract (CSE) provide sedative and anxiolytic effects. We investigate if CSE could attenuate anxiety-like behaviors induced by novelty and alarm substance exposures in zebrafish. Adult zebrafish were injected with vehicle, clonazepam, or CSE (25, 50 or 100 mg/kg) and submitted to novel tank test. At the end, saline or alarm substance was added and anxiety-like responses were recorded. Twenty-four hours after, fish were submitted to the light/dark test. Novelty associated with alarm substance exposure decreased distance traveled and total time mobile in novel tank, and CSE (at 50 and 100 mg/kg) prevented these alterations similarly to clonazepam. Alarm substance reduced the time spent in white compartment (p = 0.0193 as compared with vehicle group). Clonazepam and CSE prevented this anxiogenic effect of alarm substance. CSE presents anxiolytic effects against alarm substance-induced locomotor and anxiogenic responses similarly to clonazepam. These data corroborate with the use of this plant in traditional medicine and provides a putative new pharmacological intervention for anxiety disorders.
BioMed Research International, 2015
Depression continues to be a major global health problem. Although antidepressants are used for its treatment, efficacy is often inconsistent. Thus, the search for alternative therapeutic medicines for its treatment is still important. In this study, the antidepressant-like effect ofPseudospondias microcarpaextract (30–300 mg kg−1,p.o.) was investigated in two predictive models of depression—forced swimming test and tail suspension test in mice. Additionally, the mechanism(s) of action involved were assessed. Acute treatment with the extract dose dependently reduced immobility of mice in both models. The antidepressant-like effect of the extract (100 mg kg−1,p.o.) was blocked byp-chlorophenylalanine and cyproheptadine but not prazosin, propranolol, or yohimbine. Concomitant administration ofd-cycloserine and the extract potentiated the anti-immobility effect. In contrast,d-serine, a full agonist of glycine/NMDA receptors, abolished the effects. Anti-immobility effects of PME were pr...
Pharmacological modulation of anxiety-like phenotypes in adult zebrafish behavioral models
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2011
Zebrafish (Danio rerio) are becoming increasingly popular in neurobehavioral research. Here, we summarize recent data on behavioral responses of adult zebrafish to a wide spectrum of putative anxiolytic and anxiogenic agents. Using the novel tank test as a sensitive and efficient behavioral assay, zebrafish anxiety-like behavior can be bi-directionally modulated by drugs affecting the gamma-aminobutyric acid, monoaminergic, cholinergic, glutamatergic and opioidergic systems. Complementing human and rodent data, zebrafish drugevoked phenotypes obtained in this test support this species as a useful model for neurobehavioral and psychopharmacological research.
International Journal of Basic and Clinical Pharmacology, 2016
Background: Depression is a widespread, devastating mental illness and currently available treatments have significant limitations including low response rates and delayed onset of action. N-methyl-D-aspartate (NMDA) receptor antagonists exert fast-acting antidepressant effects. Pseudospondias microcarpa produces an antidepressant-like effect via inhibition of the glycine/NMDA receptor complex, and could therefore possess a rapid onset of action. Therefore, the present study investigated the possible rapid-onset antidepressant action of P. microcarpa in mice. Methods: In this study, rapid-onset and sustained antidepressant effects of the hydroethanolic leaf extract of P. microcarpa (PME) was investigated in the open-space swim test, a chronic model of depression. Antidepressant effect was further assessed in the tail suspension test (TST). In addition, the effect of the extract on cognitive function in the Morris water maze (MWM) test was investigated. Results: Depressed mice showed a significant increase in immobility and decrease in distance swum. However, treatment with PME and the classical antidepressants significantly decreased immobility time and increased distance swum. Furthermore, unlike the classical antidepressants which required 10-14 days to significantly improve mobility behaviour, PME treatment significantly decreased immobility time (P<0.001) on the first day of treatment (day 5 of stress procedure). This effect was also sustained for the remainder of the experiment. The extract also significantly decreased immobility time in the TST (F3,16=4.881, P=0.0135) and decreased escape latency (F4,24=12.07, P<0.0001) in the MWM procedure. Conclusions: The leaves of P. microcarpa exhibits rapid and sustained antidepressant effects and improve cognitive function in depressed mice.
Effects of Natural Monoamine Oxidase Inhibitors on Anxiety-Like Behavior in Zebrafish
Frontiers in Pharmacology, 2021
Monoamine oxidases (MAO) are a valuable class of mitochondrial enzymes with a critical role in neuromodulation. In this study, we investigated the effect of natural MAO inhibitors on novel environment-induced anxiety by using the zebrafish novel tank test (NTT). Because zebrafish spend more time at the bottom of the tank when they are anxious, anxiolytic compounds increase the time zebrafish spend at the top of the tank and vice versa. Using this paradigm, we found that harmane, norharmane, and 1,2,3,4-tetrahydroisoquinoline (TIQ) induce anxiolytic-like effects in zebrafish, causing them to spend more time at the top of the test tank and less time at the bottom. 2,3,6-trimethyl-1,4-naphtoquinone (TMN) induced an interesting mix of both anxiolytic-and anxiogenic-like effects during the first and second halves of the test, respectively. TIQ was unique in having no observable effect on general movement. Similarly, a reference MAO inhibitor clorgyline-but not pargyline-increased the time spent at the top in a concentration-dependent manner. We also demonstrated that the brain bioavailability of these compounds are high based on the ex vivo bioavailability assay and in silico prediction models, which support the notion that the observed effects on anxiety-like behavior in zebrafish were most likely due to the direct effect of these compounds in the brain. This study is the first investigation to demonstrate the anxiolytic-like effects of MAO inhibitors on novel environment-induced anxiety in zebrafish.