Antidepressant effect of PT-31, an α₂-adrenoceptor agonist, on lipopolysaccharide-induced depressive-like behavior in mice.

IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES
Behavioural Pharmacology Pub Date : 2024-09-01 Epub Date: 2024-07-19 DOI:10.1097/FBP.0000000000000785
Juliana Machado Kayser, Fernanda Petry, Maryelen Alijar Souza, Monica Santin Zanatta Schindler, Letícia Vidor Morgan, Gabriela Zimmermann Prado Rodrigues, Samara Cristina Mazon, Gean Pablo Silva Aguiar, Marina Galdino da Rocha Pitta, Ivan da Rocha Pitta, Léder Leal Xavier, Liz Girardi Müller, Günther Gehlen, Andresa Heemann Betti
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引用次数: 0

Abstract

Increasing evidence indicates that neuroinflammation, oxidative stress, and neurotrophic factors play a key role in the pathophysiology of major depressive disorder (MDD). In addition, the attenuation of inflammatory response has been considered a putative mechanism for MDD treatment. PT-31 is an imidazolidine derivative and a putative α₂-adrenoceptor agonist that has previously demonstrated antinociceptive activity. The present study aimed to investigate the effect of PT-31 on depressive-like behavior and lipopolysaccharide-induced neurochemical changes. To this end, mice received intraperitoneally saline or lipopolysaccharide (600 µg/kg), and 5 h postinjection animals were orally treated with saline, PT-31 (3, 10, and 30 mg/kg), or fluoxetine (30 mg/kg). Mice were subjected to the open field test (OFT) 6 and 24 h after lipopolysaccharide administration and to the tail suspension test (TST) 24 h postlipopolysaccharide. Subsequently, animals were euthanized, and brains were dissected for neurochemical analyses. The administration of lipopolysaccharide-induced sickness- and depressive-like behaviors, besides promoting an increase in myeloperoxidase activity and a reduction in brain-derived neurotrophic factor (BDNF) levels. Noteworthy, PT-31 3 mg/kg attenuated lipopolysaccharide-induced decreased locomotor activity 6 h after lipopolysaccharide in the OFT. All tested doses of PT-31 significantly reduced the immobility time of animals in the TST and attenuated lipopolysaccharide-induced increased myeloperoxidase activity in the cortex of mice. Our results demonstrate that PT-31 ameliorates behavioral changes promoted by lipopolysaccharide in OFT and TST, which is possibly mediated by attenuation of the inflammatory response.

α₂-肾上腺素受体激动剂 PT-31 对脂多糖诱导的小鼠抑郁样行为的抗抑郁作用
越来越多的证据表明,神经炎症、氧化应激和神经营养因子在重度抑郁症(MDD)的病理生理学中起着关键作用。此外,减轻炎症反应也被认为是治疗重度抑郁症的一种假定机制。PT-31 是一种咪唑烷衍生物,也是一种推定的 α₂-肾上腺素受体激动剂,曾被证明具有抗痛觉活性。本研究旨在探讨 PT-31 对抑郁样行为和脂多糖诱导的神经化学变化的影响。为此,小鼠腹腔注射生理盐水或脂多糖(600 µg/kg),注射后 5 小时口服生理盐水、PT-31(3、10 和 30 mg/kg)或氟西汀(30 mg/kg)。给小鼠注射脂多糖后 6 小时和 24 小时进行开阔地试验(OFT),注射脂多糖后 24 小时进行尾悬试验(TST)。随后,动物被安乐死,并剖开大脑进行神经化学分析。除了促进髓过氧化物酶活性的增加和脑源性神经营养因子(BDNF)水平的降低外,给予脂多糖还诱发了病态和抑郁样行为。值得注意的是,PT-31 3 毫克/千克可减轻脂多糖诱导的 OFT 在脂多糖诱导 6 小时后运动活动的减少。所有测试剂量的 PT-31 都能明显缩短动物在 TST 中的静止时间,并减轻脂多糖引起的小鼠皮层髓过氧化物酶活性的升高。我们的研究结果表明,PT-31 可改善脂多糖引起的 OFT 和 TST 行为变化,这可能是通过减轻炎症反应介导的。
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来源期刊
Behavioural Pharmacology
Behavioural Pharmacology 医学-行为科学
CiteScore
3.40
自引率
0.00%
发文量
84
审稿时长
6-12 weeks
期刊介绍: Behavioural Pharmacology accepts original full and short research reports in diverse areas ranging from ethopharmacology to the pharmacology of schedule-controlled operant behaviour, provided that their primary focus is behavioural. Suitable topics include drug, chemical and hormonal effects on behaviour, the neurochemical mechanisms under-lying behaviour, and behavioural methods for the study of drug action. Both animal and human studies are welcome; however, studies reporting neurochemical data should have a predominantly behavioural focus, and human studies should not consist exclusively of clinical trials or case reports. Preference is given to studies that demonstrate and develop the potential of behavioural methods, and to papers reporting findings of direct relevance to clinical problems. Papers making a significant theoretical contribution are particularly welcome and, where possible and merited, space is made available for authors to explore fully the theoretical implications of their findings. Reviews of an area of the literature or at an appropriate stage in the development of an author’s own work are welcome. Commentaries in areas of current interest are also considered for publication, as are Reviews and Commentaries in areas outside behavioural pharmacology, but of importance and interest to behavioural pharmacologists. Behavioural Pharmacology publishes frequent Special Issues on current hot topics. The editors welcome correspondence about whether a paper in preparation might be suitable for inclusion in a Special Issue.
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