Nikhilesh P Paliwal, Brijesh G Taksande, Shirish P Jain, Sachin P Borikar
{"title":"GABA能系统可能参与阿片碱介导的大鼠中枢杏仁核的镇痛作用。","authors":"Nikhilesh P Paliwal, Brijesh G Taksande, Shirish P Jain, Sachin P Borikar","doi":"10.1080/00207454.2023.2268262","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>To study the pharmacological interactions between agmatine and gamma aminobutyric acid (GABA) modulatory agents in the regulation of anxiety-like behavior in rats.</p><p><strong>Materials and methods: </strong>Male Wistar rats were treated drugs per se or in combination and 15 min after last injection were subjected to elevated plus-maze (EPM) test. Anxiety-like behavior was evaluated by measuring behavioral conventional readout, open arm activity (duration and/or entries) for 5-minute duration.</p><p><strong>Results: </strong>Acute intra-central amygdala (CeA) injection of agmatine (0.1-0.6 μmol/site/rat), muscimol (0.25-1 nmol/site/rat), diazepam (5-20 μg/site/rat) and allopregnanolone (2-8 μg/site/rat) increased open arm entries of the rats in EPM suggesting anxiolytic effect in dose dependent manner. Moreover, the anxiolytic effect at subeffective dose of agmatine (0.1 μmol/site/rat) was potentiated by subeffective dose of muscimol (0.25 nmol/site/rat), diazepam (5 μg/site/rat) and allopregnanolone (4 μg/site/rat). Whereas, pretreatment with GABA<sub>A</sub> receptor antagonist, bicuculline (10 ng/site/rat) blocked the anxiolytic effect of agmatine and its synergistic effect of agmatine plus muscimol. Similarly, benzodiazepine (BZD) receptor antagonist, flumazenil (15 μg/site/rat) and GABA allosteric modulator antagonist, RO 15-45 13 (10 μg/site/rat) reduced the anxiolytic effect of agmatine, given alone and with diazepam and allopregnanolone, respectively.</p><p><strong>Conclusion: </strong>These results indicated that anxiolytic effect of agmatine is medicated via GABAergic mechanisms, probably conciliated by the GABA<sub>A</sub> receptor subtypes. Modulation of interplay between agmatine and GABA<sub>A</sub> receptor activity might be a pertinent solution for the regulation of anxiety.</p>","PeriodicalId":14161,"journal":{"name":"International Journal of Neuroscience","volume":" ","pages":"1346-1356"},"PeriodicalIF":1.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Possible involvement of GABAergic system on central amygdala Mediated anxiolytic effect of agmatine in rats.\",\"authors\":\"Nikhilesh P Paliwal, Brijesh G Taksande, Shirish P Jain, Sachin P Borikar\",\"doi\":\"10.1080/00207454.2023.2268262\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>To study the pharmacological interactions between agmatine and gamma aminobutyric acid (GABA) modulatory agents in the regulation of anxiety-like behavior in rats.</p><p><strong>Materials and methods: </strong>Male Wistar rats were treated drugs per se or in combination and 15 min after last injection were subjected to elevated plus-maze (EPM) test. Anxiety-like behavior was evaluated by measuring behavioral conventional readout, open arm activity (duration and/or entries) for 5-minute duration.</p><p><strong>Results: </strong>Acute intra-central amygdala (CeA) injection of agmatine (0.1-0.6 μmol/site/rat), muscimol (0.25-1 nmol/site/rat), diazepam (5-20 μg/site/rat) and allopregnanolone (2-8 μg/site/rat) increased open arm entries of the rats in EPM suggesting anxiolytic effect in dose dependent manner. Moreover, the anxiolytic effect at subeffective dose of agmatine (0.1 μmol/site/rat) was potentiated by subeffective dose of muscimol (0.25 nmol/site/rat), diazepam (5 μg/site/rat) and allopregnanolone (4 μg/site/rat). Whereas, pretreatment with GABA<sub>A</sub> receptor antagonist, bicuculline (10 ng/site/rat) blocked the anxiolytic effect of agmatine and its synergistic effect of agmatine plus muscimol. Similarly, benzodiazepine (BZD) receptor antagonist, flumazenil (15 μg/site/rat) and GABA allosteric modulator antagonist, RO 15-45 13 (10 μg/site/rat) reduced the anxiolytic effect of agmatine, given alone and with diazepam and allopregnanolone, respectively.</p><p><strong>Conclusion: </strong>These results indicated that anxiolytic effect of agmatine is medicated via GABAergic mechanisms, probably conciliated by the GABA<sub>A</sub> receptor subtypes. Modulation of interplay between agmatine and GABA<sub>A</sub> receptor activity might be a pertinent solution for the regulation of anxiety.</p>\",\"PeriodicalId\":14161,\"journal\":{\"name\":\"International Journal of Neuroscience\",\"volume\":\" \",\"pages\":\"1346-1356\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/00207454.2023.2268262\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/10/24 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q4\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00207454.2023.2268262","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/24 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Possible involvement of GABAergic system on central amygdala Mediated anxiolytic effect of agmatine in rats.
Objectives: To study the pharmacological interactions between agmatine and gamma aminobutyric acid (GABA) modulatory agents in the regulation of anxiety-like behavior in rats.
Materials and methods: Male Wistar rats were treated drugs per se or in combination and 15 min after last injection were subjected to elevated plus-maze (EPM) test. Anxiety-like behavior was evaluated by measuring behavioral conventional readout, open arm activity (duration and/or entries) for 5-minute duration.
Results: Acute intra-central amygdala (CeA) injection of agmatine (0.1-0.6 μmol/site/rat), muscimol (0.25-1 nmol/site/rat), diazepam (5-20 μg/site/rat) and allopregnanolone (2-8 μg/site/rat) increased open arm entries of the rats in EPM suggesting anxiolytic effect in dose dependent manner. Moreover, the anxiolytic effect at subeffective dose of agmatine (0.1 μmol/site/rat) was potentiated by subeffective dose of muscimol (0.25 nmol/site/rat), diazepam (5 μg/site/rat) and allopregnanolone (4 μg/site/rat). Whereas, pretreatment with GABAA receptor antagonist, bicuculline (10 ng/site/rat) blocked the anxiolytic effect of agmatine and its synergistic effect of agmatine plus muscimol. Similarly, benzodiazepine (BZD) receptor antagonist, flumazenil (15 μg/site/rat) and GABA allosteric modulator antagonist, RO 15-45 13 (10 μg/site/rat) reduced the anxiolytic effect of agmatine, given alone and with diazepam and allopregnanolone, respectively.
Conclusion: These results indicated that anxiolytic effect of agmatine is medicated via GABAergic mechanisms, probably conciliated by the GABAA receptor subtypes. Modulation of interplay between agmatine and GABAA receptor activity might be a pertinent solution for the regulation of anxiety.
期刊介绍：
The International Journal of Neuroscience publishes original research articles, reviews, brief scientific reports, case studies, letters to the editor and book reviews concerned with problems of the nervous system and related clinical studies, epidemiology, neuropathology, medical and surgical treatment options and outcomes, neuropsychology and other topics related to the research and care of persons with neurologic disorders. The focus of the journal is clinical and transitional research. Topics covered include but are not limited to: ALS, ataxia, autism, brain tumors, child neurology, demyelinating diseases, epilepsy, genetics, headache, lysosomal storage disease, mitochondrial dysfunction, movement disorders, multiple sclerosis, myopathy, neurodegenerative diseases, neuromuscular disorders, neuropharmacology, neuropsychiatry, neuropsychology, pain, sleep disorders, stroke, and other areas related to the neurosciences.
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