Possible involvement of GABAergic system on central amygdala Mediated anxiolytic effect of agmatine in rats.

IF 1.7 4区医学 Q4 NEUROSCIENCES International Journal of Neuroscience Pub Date : 2024-11-01 Epub Date: 2023-10-24 DOI:10.1080/00207454.2023.2268262

Nikhilesh P Paliwal, Brijesh G Taksande, Shirish P Jain, Sachin P Borikar

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Abstract

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 GABA_A 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 GABA_A receptor subtypes. Modulation of interplay between agmatine and GABA_A receptor activity might be a pertinent solution for the regulation of anxiety.

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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。

在这项研究中，胍丁胺和修饰γ-氨基丁酸（GABA）的药物之间的药理学相互作用，以及它们在调节焦虑样行为中的作用，已经在使用高架+迷宫的大鼠中进行了广泛的研究。我们发现，急性中央杏仁核内注射Agmatine（0.1-0.6µmol/site/只大鼠）、Muscimol（0.25-1 nmol/site/大鼠）、地西泮（5-20µg/site/大白鼠）和异孕烯醇酮（2-8µg/位点/大白鼠。亚有效剂量的胍丁胺（0.1µmol/位点/大鼠）的抗焦虑作用被亚有效剂量（0.25 nmol/site/大鼠）、地西泮（5µg/site/大白鼠）和阿洛孕纳龙（4µg/site/大白鼠。GABAA受体拮抗剂荷包牡丹碱（10 ng/site/大鼠）阻断胍丁胺的抗焦虑作用及其胍丁胺与麝香草酚的协同作用。类似地，BZD受体拮抗剂Flumazenil（15µg/位点/大鼠）和GABA变构调节剂拮抗剂RO 15-45 13（10µg/位点-大鼠）分别降低了单独给药以及与地西泮和别孕纳龙联合给药的胍丁胺的抗焦虑作用。这些结果表明，胍丁胺的抗焦虑作用是通过GABAA能机制来治疗的，可能与GABAA受体亚型有关。调节胍丁胺和GABAA受体活性之间的相互作用可能是调节焦虑的相关解决方案。

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来源期刊

International Journal of Neuroscience 医学-神经科学

CiteScore

5.10

自引率

0.00%

发文量

132

审稿时长

2 months

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.