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Antidepressive synergism between crocin and D-AP5 in acute restraint-stressed mice. 巴豆素和 D-AP5 在急性束缚应激小鼠中的抗抑郁协同作用
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-07-15 DOI: 10.1097/FBP.0000000000000784
Sana-Sadat Gerami, Mohaddeseh Ebrahimi-Ghiri, Fatemeh Khakpai, Mohammad-Reza Zarrindast

Emerging evidence suggests that crocin rescues stress-induced depressive symptoms in mice via stimulation of hippocampal neurogenesis. Glutamate modulators mainly involving N-methyl- d -aspartate (NMDA) receptors (NMDARs) have highlighted a role in neural development, synaptic plasticity, and depression. The research presented here was designed to appraise the interaction between NMDAR agents and crocin on depressive-related behaviors in the NMRI male mice exposed to acute restraint stress (ARS) for a period of 4 h. The mice were submitted to the splash test, forced swimming test, and tail suspension test to evaluate depressive-like behavior. The ARS decreased the grooming duration in the splash test and increased immobility time in the forced swimming test and tail suspension test, suggesting a depressive-like phenotype. NMDA (0.25 and 0.5 μg/mouse, intracerebroventricular) did not alter depression-related profiles in both non-acute restraint stress (NARS) and ARS mice, while the same doses of NMDAR antagonist D-AP5 potentiated the antidepressive-like activities in the ARS mice compared with the NARS mice. Moreover, a low dose of NMDA did not change depression-related parameters in the crocin-treated NARS or ARS mice, while D-AP5 enhanced the crocin response in the NARS and ARS mice. Isobologram analysis noted a synergism between crocin and D-AP5 on antidepressive-like behavior in the NARS and ARS mice. Collectively, the combination of crocin and D-AP5 was shown to mitigate depression symptoms and can be potentially used for the treatment of depression disorders.

新的证据表明,巴豆素能通过刺激海马神经发生来缓解压力诱发的小鼠抑郁症状。主要涉及 N-甲基-d-天冬氨酸(NMDA)受体(NMDARs)的谷氨酸调节剂在神经发育、突触可塑性和抑郁中发挥着重要作用。本文介绍的研究旨在评估 NMDAR 药物和巴豆苷对暴露于急性束缚应激(ARS)4 小时的 NMRI 雄性小鼠抑郁相关行为的交互作用。对小鼠进行泼水试验、强迫游泳试验和悬尾试验,以评估类似抑郁的行为。急性束缚应激减少了溅水试验中的梳理时间,增加了强迫游泳试验和悬尾试验中的不动时间,这表明小鼠出现了抑郁样表型。NMDA(0.25 和 0.5 μg/只小鼠,脑室内)不会改变非急性束缚应激(NARS)小鼠和 ARS 小鼠的抑郁相关特征,而与 NARS 小鼠相比,相同剂量的 NMDAR 拮抗剂 D-AP5 会增强 ARS 小鼠的抗抑郁样活动。此外,低剂量的 NMDA 不会改变经巴豆毒素处理的 NARS 或 ARS 小鼠的抑郁相关参数,而 D-AP5 则会增强 NARS 和 ARS 小鼠对巴豆毒素的反应。等全息图分析表明,巴豆素和 D-AP5 对 NARS 和 ARS 小鼠的抗抑郁行为具有协同作用。总之,黄花霉素和 D-AP5 的组合可减轻抑郁症状,有望用于抑郁症的治疗。
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引用次数: 0
Antidepressant-like effect of riparin I and riparin II against CUMS-induced neuroinflammation via astrocytes and microglia modulation in mice. 瑞香素 I 和瑞香素 II 通过调节小鼠星形胶质细胞和小胶质细胞对 CUMS 诱导的神经炎症具有抗抑郁样作用。
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-07-19 DOI: 10.1097/FBP.0000000000000788
Iardja S L Sales, Alana G de Souza, Adriano J M Chaves Filho, Tiago L Sampaio, Daniel M A da Silva, José T Valentim, Raquell de C Chaves, Michelle V R Soares, Dilailson C Costa Júnior, José M Barbosa Filho, Danielle S Macêdo, Francisca Cléa Florenço de Sousa

Depression is a common mood disorder and many patients do not respond to conventional pharmacotherapy or experience a variety of adverse effects. This work proposed that riparin I (RIP I) and riparin II (RIP II) present neuroprotective effects through modulation of astrocytes and microglia, resulting in the reversal of depressive-like behaviors. To verify our hypothesis and clarify the pathways underlying the effect of RIP I and RIP II on neuroinflammation, we used the chronic unpredictable mild stress (CUMS) depression model in mice. Male Swiss mice were exposed to stressors for 28 days. From 15 th to the 22 nd day, the animals received RIP I or RIP II (50 mg/kg) or fluoxetine (FLU, 10 mg/kg) or vehicle, by gavage. On the 29 th day, behavioral tests were performed. Expressions of microglia (ionized calcium-binding adaptor molecule-1 - Iba-1) and astrocyte (glial fibrillary acidic protein - GFAP) markers and levels of cytokines tumor necrosis factor alfa (TNF-α) and interleukin 1 beta (IL-1β) were measured in the hippocampus. CUMS induced depressive-like behaviors and cognitive impairment, high TNF-α and IL-1β levels, decreased GFAP, and increased Iba-1 expressions. RIP I and RIP II reversed these alterations. These results contribute to the understanding the mechanisms underlying the antidepressant effect of RIP I and RIP II, which may be related to neuroinflammatory suppression.

抑郁症是一种常见的情绪障碍,许多患者对传统药物疗法没有反应,或出现各种不良反应。这项研究提出,瑞香素 I(RIP I)和瑞香素 II(RIP II)通过调节星形胶质细胞和小胶质细胞发挥神经保护作用,从而逆转抑郁样行为。为了验证我们的假设并阐明 RIP I 和 RIP II 对神经炎症的影响途径,我们使用了慢性不可预知轻度应激(CUMS)抑郁小鼠模型。雄性瑞士小鼠暴露于应激源 28 天。从第 15 天到第 22 天,动物通过灌胃接受 RIP I 或 RIP II(50 毫克/千克)或氟西汀(FLU,10 毫克/千克)或载体。第 29 天,进行行为测试。在海马中测量了小胶质细胞(离子化钙结合适配分子-1 - Iba-1)和星形胶质细胞(胶质纤维酸性蛋白 - GFAP)标记物的表达以及细胞因子肿瘤坏死因子α(TNF-α)和白细胞介素1β(IL-1β)的水平。CUMS诱导了抑郁样行为和认知障碍、高TNF-α和IL-1β水平、GFAP减少和Iba-1表达增加。RIP I和RIP II可逆转这些改变。这些结果有助于理解RIP I和RIP II抗抑郁作用的机制,这可能与神经炎症抑制有关。
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引用次数: 0
Stimulation of central histaminergic transmission attenuates diazepam-induced motor disturbance on rota-rod and beam walking tests in mice. 刺激中枢组胺能传导可减轻地西泮引起的小鼠轱辘杆和横梁行走试验的运动障碍。
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-09-01 Epub Date: 2024-07-19 DOI: 10.1097/FBP.0000000000000786
Richa Patel, Nishant Sudhir Jain

Diazepam administration has been shown to influence the release of histamine in various brain areas involved in motor behavior. Therefore, the present study explored the plausible regulatory role of the central histaminergic system in diazepam-induced deficits in motor performance in mice using the rota-rod and beam walking tests. In this study, several doses of diazepam (0.5, 1, 2, and 3 mg/kg, i.p.) were assessed in mice for changes in motor performance on the rota-rod and beam walking test. In addition, the brain histamine levels were determined after diazepam administration, and the diazepam-induced motor deficits were assessed in mice, pretreated centrally (intracerebroventricular) with histaminergic agents such as histamine (0.1, 10 µg), histamine precursor (L-histidine: 0.1, 2.5 µg), histamine neuronal releaser/H 3 receptor antagonist (thioperamide: 0.5, 10 µg), H 1 and H 2 receptor agonist [2-(3-trifluoromethylphenyl) histamine (FMPH: 0.1, 6.5 µg; amthamine: 0.1, 5 µg)/antagonist (H 1 : cetirizine 0.1 µg) and (H 2 : ranitidine: 50 µg)]. Results indicate that mice treated with diazepam at doses 1, 2 mg/kg, i.p. significantly increased the brain histamine levels. Moreover, in mice pretreated with histaminergic transmission-enhancing agents, the diazepam (2 mg/kg, i.p.)-induced motor incoordination was significantly reversed. Contrastingly, diazepam (1 mg/kg, i.p.) in its subeffective dose produced significant motor deficits in mice preintracerebroventricular injected with histamine H 1 and H 2 receptor antagonists on both the employed tests. Therefore, it is postulated that endogenous histamine operates via H 1 and H 2 receptor activation to alleviate the motor-impairing effects of diazepam.

研究表明,服用地西泮会影响涉及运动行为的多个脑区的组胺释放。因此,本研究使用rota-rod和横梁行走试验,探讨了中枢组胺能系统在地西泮诱导的小鼠运动能力缺陷中可能发挥的调节作用。本研究评估了不同剂量地西泮(0.5、1、2和3毫克/千克,静脉注射)对小鼠在轮杆和横梁行走试验中运动表现的影响。此外,还测定了地西泮给药后的脑组胺水平,并评估了地西泮诱导的小鼠运动障碍,这些小鼠经中枢(脑室内)预处理后使用了组胺能药物,如组胺(0.1、10 µg)、组胺前体(L-组氨酸:0.1,2.5 µg)、组胺神经元释放剂/H3 受体拮抗剂(硫普酰胺:0.5,10 µg)、H1 和 H2 受体激动剂[2-(3-三氟甲基苯基)组胺(FMPH:0.1,6.5 µg;氨茶碱:0.1,5 µg)/拮抗剂(H1:西替利嗪 0.1 µg)和(H2:雷尼替丁:50 µg)]。结果表明,以 1、2 毫克/千克的剂量给小鼠静脉注射地西泮会显著增加脑组胺水平。此外,在使用组胺能传递增强剂预处理的小鼠中,地西泮(2 毫克/千克,静注)诱导的运动不协调被明显逆转。相反,在小鼠脑室注射组胺 H1 和 H2 受体拮抗剂前,次有效剂量的地西泮(1 毫克/千克,静注)会在两种测试中产生明显的运动障碍。因此,可以推测内源性组胺是通过激活 H1 和 H2 受体来减轻地西泮的运动损伤作用的。
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引用次数: 0
Antidepressant effect of PT-31, an α₂-adrenoceptor agonist, on lipopolysaccharide-induced depressive-like behavior in mice. 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
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES 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

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.

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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引用次数: 0
New insights about the antidepressant-like effects of riparin A in a chronic murine model of depression. 里帕林 A 在慢性抑郁症小鼠模型中的抗抑郁样作用的新见解。
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-11 DOI: 10.1097/FBP.0000000000000781
Cássio Prinholato da Silva, Denise Dias Oliveira, Bruno Iglesias Benincasa, Bruna Barbar, Raphaela Gonçalves Barros Perri, Ana Lúcia Fachin, Luiz Luciano Falconi-Sobrinho, Rene Oliveira Beleboni

Riparin A is a synthetic form of natural riparins. Acute scale studies that take into consideration the structure-activity relationship have shown preliminary evidence of antidepressant and anxiolytic effects of riparin A, similar to that already known for other riparins. However, for better pharmacological characterization of this new compound, further studies are required. The aim of this work was to evaluate the effect of chronic treatment with riparin A (10 mg/kg; intraperitoneally) on depressive-like behavior in the forced swimming test and tail suspension test, as well as the reduction of anhedonia in the sucrose preference test, and on anxiety-like behavior in the open field and elevated plus maze apparatus, triggered in rats previously subjected to unpredictable chronic mild stress by 4 weeks. In addition, a pentobarbital-induced sleep time test was also used. Riparin A reduced the duration of immobility in both the forced swimming test and tail suspension test, as well as attenuated the anhedonia in the sucrose preference test. Furthermore, riparin A appears to produce anxiolytic effects in rats exposed to an open field and elevated plus maze, while increasing the alertness/vigilance in rats submitted to pentobarbital-induced sleep time test, without altering their locomotor integrity. Our results suggest that chronic riparin A appears to be a potential pharmacological target for new studies on the control of depression- and anxiety-like behaviors in stressed rats.

瑞香素 A 是天然瑞香素的合成形式。考虑到结构-活性关系的急性规模研究显示,有初步证据表明瑞香素 A 具有抗抑郁和抗焦虑作用,与已知的其他瑞香素相似。然而,为了更好地描述这种新化合物的药理特征,还需要进一步的研究。这项工作的目的是评估长期服用瑞香素 A(10 毫克/千克;腹腔注射)对大鼠在强迫游泳试验和悬尾试验中的抑郁样行为、蔗糖偏好试验中的失神以及在开放场地和高架加迷宫装置中的焦虑样行为的影响。此外,还使用了戊巴比妥诱导睡眠时间测试。瑞帕灵 A 可缩短强迫游泳试验和尾悬试验中的不动持续时间,并减轻蔗糖偏好试验中的失神状态。此外,瑞香素 A 似乎还能对暴露于开放场地和高架加迷宫的大鼠产生抗焦虑作用,同时提高接受戊巴比妥诱导睡眠时间试验的大鼠的警觉性/警惕性,而不改变其运动完整性。我们的研究结果表明,长期服用瑞香素 A 似乎是一种潜在的药理学靶点,可用于控制应激大鼠的抑郁和焦虑类行为的新研究。
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引用次数: 0
Pain-suppressed consumption of highly palatable liquid in rats. 大鼠在疼痛抑制下食用高味液体
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-07 DOI: 10.1097/FBP.0000000000000783
Rebecca M Craft

This study determined whether consumption of a highly palatable liquid is a reliable measure of inflammatory pain and antinociception in male and female rats. After a 10-day acquisition period, the impact of intraplantar oil vs. complete Freund adjuvant (CFA) on consumption of vanilla-flavored Ensure was assessed, with a sipper tube height 12 or 19 cm above the floor. CFA significantly decreased Ensure consumption, which completely recovered within 4-7 days to levels in oil-treated controls; neither sex nor sipper tube height significantly influenced Ensure consumption. CFA also significantly suppressed Ensure consumption in rats not exposed to the 10-day acquisition period, but only in males. To test the predictive validity of Ensure consumption as a measure of pain, separate rats were pretreated with a vehicle, an opioid, a nonsteroidal anti-inflammatory drug, or a cannabinoid the day after CFA treatment. Morphine and ibuprofen significantly attenuated CFA-suppressed drinking in at least one sex, and tetrahydrocannabinol did not. Neither ibuprofen nor tetrahydrocannabinol significantly altered drinking in oil-injected, 'pain-free' controls, but morphine increased drinking. These results demonstrate that CFA decreases consumption of a highly palatable liquid regardless of previous exposure (training) to the consumption procedure, but only in males. Although standard analgesics attenuate CFA-suppressed drinking, nonspecific hyperphagic effects can confound the interpretation of results. Thus, consumption of a highly palatable liquid is not an optimal measure for candidate analgesic screening.

本研究确定了食用高适口性液体是否是衡量雄性和雌性大鼠炎性疼痛和抗痛觉的可靠指标。在经过 10 天的习得期后,评估了胰腺内油与完全弗氏佐剂(CFA)对香草味 Ensure 消费量的影响,啜饮管的高度为离地面 12 厘米或 19 厘米。CFA明显降低了Ensure的消耗量,但在4-7天内完全恢复到了油处理对照组的水平;性别和吸管高度对Ensure的消耗量均无明显影响。CFA 还明显抑制了未暴露于 10 天习得期的大鼠的 Ensure 消费量,但仅限于雄性大鼠。为了测试 Ensure 消耗量作为疼痛测量指标的预测有效性,在 CFA 处理后的第二天分别对大鼠进行了载体、阿片类药物、非甾体抗炎药或大麻素的预处理。吗啡和布洛芬至少对一种性别的大鼠有明显的抑制作用,而四氢大麻酚则没有。布洛芬和四氢大麻酚都不会明显改变注射了 "无痛 "油的对照组的饮酒量,但吗啡会增加饮酒量。这些结果表明,无论以前是否接触过(训练过)饮用高适口性液体的过程,CFA 都会降低饮用量,但仅限于男性。尽管标准镇痛剂会减轻CFA抑制的饮水量,但非特异性的吞咽功能亢进效应会混淆结果的解释。因此,饮用高适口性液体并不是筛选候选镇痛药的最佳方法。
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引用次数: 0
Propranolol attenuates the establishment of conditioned context aversions: differential effects compared to MK-801 in an animal model of anticipatory nausea and vomiting. 普萘洛尔减弱条件性情境厌恶的建立:在预期恶心和呕吐动物模型中与 MK-801 相比的不同效果。
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-07 DOI: 10.1097/FBP.0000000000000779
Çinar Furkan İlhan, Esra Ülke, Gonzalo P Urcelay, Sezen Kişlal

Cancer patients often experience anticipatory nausea and vomiting (ANV) due to Pavlovian conditioning. Both N-methyl-D-aspartate and beta-adrenergic receptors are known to mediate memory formation, but their role in the development of ANV remains unclear. This study used a conditioned context aversion (CCA) paradigm, an animal model for ANV, to assess whether administration of the beta-adrenergic receptor antagonist propranolol or the N-methyl-D-aspartate receptor antagonist MK-801 immediately after CCA training has an effect on the later expression of CCA in CD1 male mice. In experiment 1, three groups were injected with lithium chloride (LiCl) to induce aversion in a novel context, resulting in CCA. A control group was injected with sodium chloride (NaCl). Following conditioning, two of the LiCl-treated groups received different doses of MK-801 (0.05 or 0.2 mg/kg), while the remaining LiCl-treated and NaCl-treated groups received a second NaCl injection. In experiment 2, two groups were injected with LiCl, and one group was injected with NaCl. After conditioning, one of the LiCl-treated groups received a propranolol injection (10 mg/kg). The remaining LiCl-treated and NaCl-treated groups received NaCl injections. Water consumption was measured in all groups 72 h later within the conditioning context. Postconditioning administration of propranolol, but not MK-801, attenuated CCA, as revealed by similar levels of water consumption in animals that received LiCl and propranolol relative to NaCl-treated animals. These findings suggest that beta-adrenergic receptor activation is crucial for the development of CCA. Therefore, propranolol may represent a novel therapeutic approach for cancer patients at high risk of ANV.

癌症患者经常会因巴甫洛夫条件反射而出现预期性恶心和呕吐(ANV)。已知N-甲基-D-天冬氨酸受体和β-肾上腺素能受体都能介导记忆的形成,但它们在恶心呕吐发生过程中的作用仍不清楚。本研究使用条件性情境厌恶(CCA)范例(ANV的动物模型)来评估在CCA训练后立即给予β肾上腺素能受体拮抗剂普萘洛尔或N-甲基-D-天冬氨酸受体拮抗剂MK-801是否会影响CD1雄性小鼠日后的CCA表达。在实验 1 中,三组小鼠被注射氯化锂(LiCl),以诱导小鼠在新环境中产生厌恶感,从而导致 CCA。对照组注射氯化钠(NaCl)。调节后,氯化锂处理组中的两组接受不同剂量的 MK-801(0.05 或 0.2 毫克/千克),其余氯化锂处理组和氯化钠处理组接受第二次氯化钠注射。在实验 2 中,两组注射氯化锂,一组注射氯化钠。调节后,锂盐处理组中的一组接受普萘洛尔注射(10 毫克/千克)。其余的氯化锂处理组和氯化钠处理组则注射氯化钠。72 小时后,在调节背景下测量所有组的耗水量。与接受氯化锂和普萘洛尔治疗的动物相比,接受氯化钠和普萘洛尔治疗的动物的耗水量水平相似,这表明普萘洛尔而非 MK-801 可减轻条件反射后的 CCA。这些研究结果表明,β肾上腺素能受体的激活对 CCA 的发展至关重要。因此,普萘洛尔可能是治疗高危癌症患者的一种新方法。
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引用次数: 0
A novel tramadol-polycaprolactone implant could palliate heroin conditioned place preference and withdrawal in rats: behavioral and neurochemical study. 一种新型曲马多-聚己内酯植入物可缓解大鼠的海洛因条件性位置偏好和戒断:行为和神经化学研究。
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-17 DOI: 10.1097/FBP.0000000000000778
Shaimaa A Elshebiney, Rania A Elgohary, Marwa E El-Shamarka, Mostafa Mabrouk, Hanan H Beheri

Drug dependence is a chronic brain disease characterized by craving and recurrent episodes of relapse. Tramadol HCl is a promising agent for withdrawal symptoms management, considering its relatively low abuse potential and safety. Oral administration, however, is not preferred in abstinence maintenance programs. Introducing an implantable, long-lasting formula is suggested to help outpatient abstinence programs achieve higher rates of treatment continuation. Tramadol implants (T350 and T650) were prepared on polycaprolactone polymer ribbons by the wet method. Male Wistar rats were adapted to heroin-conditioned place preference (CPP) at escalating doses (3-30 mg/kg, intraperitoneally, for 14 days). Implants were surgically implanted in the back skin of rats. After 14 days, the CPP score was recorded. Naloxone (1 mg/kg, intraperitoneally) was used to induce withdrawal on day 15, and symptoms were scored. Elevated plus maze and open field tests were performed for anxiety-related symptoms. Striata were analyzed for neurochemical changes reflected in dopamine, 3,4-dihydroxyphenyl acetic acid, gamma-aminobutyric acid, and serotonin levels. Brain oxidative changes including glutathione and lipid peroxides were assessed. The tramadol implants (T350 and T650) reduced heroin CPP and limited naloxone-induced withdrawal symptoms. The striata showed increased levels of 3,4-dihydroxyphenyl acetic acid, and serotonin and decreased levels of gamma-aminobutyric acid and dopamine after heroin withdrawal induction, which were reversed after implanting T350 and T650. Implants restore the brain oxidative state. Nonsignificant low naloxone-induced withdrawal score after the implant was used in naive subjects indicating low abuse potential of the implants. The presented tramadol implants were effective at diminishing heroin CPP and withdrawal in rats, suggesting further investigations for application in the management of opioid withdrawal.

药物依赖是一种慢性脑部疾病,其特点是渴求和反复复发。考虑到盐酸曲马多的滥用可能性相对较低且安全性高,它是一种很有前景的戒断症状控制药物。然而,在戒断维持计划中,口服给药并不是首选。建议引入一种可植入的长效配方,以帮助门诊戒断计划实现更高的持续治疗率。采用湿法在聚己内酯聚合物带上制备曲马多植入剂(T350 和 T650)。雄性 Wistar 大鼠以递增剂量(3-30 毫克/千克,腹腔注射,14 天)适应海洛因条件性场所偏好(CPP)。植入物通过手术植入大鼠背部皮肤。14 天后,记录 CPP 评分。第 15 天使用纳洛酮(1 毫克/千克,腹腔注射)诱导戒断,并对症状进行评分。对焦虑相关症状进行高架加迷宫和开阔地测试。分析纹状体的神经化学变化,以反映多巴胺、3,4-二羟基苯乙酸、γ-氨基丁酸和血清素的水平。还对包括谷胱甘肽和脂质过氧化物在内的大脑氧化变化进行了评估。曲马多植入物(T350和T650)降低了海洛因的CPP,并限制了纳洛酮诱发的戒断症状。植入 T350 和 T650 后,海洛因戒断诱导的纹状体中 3,4-二羟基苯乙酸和血清素水平升高,γ-氨基丁酸和多巴胺水平降低。植入物可恢复大脑氧化状态。在天真的受试者中使用植入物后,纳洛酮诱导的戒断评分并不显著降低,这表明植入物的滥用可能性较低。所展示的曲马多植入物能有效降低大鼠的海洛因CPP和戒断率,建议进一步研究其在阿片类药物戒断管理中的应用。
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引用次数: 0
Comparing withdrawal- and anxiety-like behaviors following oral and subcutaneous oxycodone administration in C57BL/6 mice. 比较 C57BL/6 小鼠口服和皮下注射羟考酮后的戒断和焦虑行为。
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-03 DOI: 10.1097/FBP.0000000000000780
Suzannah S De Almeida, Caryssa R Drinkuth, Gregory C Sartor

Excessive prescribing and misuse of prescription opioids, such as oxycodone, significantly contributed to the current opioid crisis. Although oxycodone is typically consumed orally by humans, parenteral routes of administration have primarily been used in preclinical models of oxycodone dependence. To address this issue, more recent studies have used oral self-administration procedures to study oxycodone seeking and withdrawal in rodents. Behavioral differences, however, following oral oxycodone intake versus parenteral oxycodone administration remain unclear. Thus, the goal of the current studies was to compare anxiety- and withdrawal-like behaviors using established opioid dependence models of either home cage oral intake of oxycodone (0.5 mg/ml) or repeated subcutaneous (s.c.) injections of oxycodone (10 mg/kg) in male and female mice. Here, mice received 10 days of oral or s.c. oxycodone administration, and following 72 h of forced abstinence, anxiety- and withdrawal-like behaviors were measured using elevated zero maze, open field, and naloxone-induced precipitated withdrawal procedures. Global withdrawal scores were increased to a similar degree following oral and s.c. oxycodone use, while both routes of oxycodone administration had minimal effects on anxiety-like behaviors. When examining individual withdrawal-like behaviors, mice receiving s.c. oxycodone exhibited more paw tremors and jumps during naloxone-induced precipitated withdrawal compared with oral oxycodone mice. These results indicate that both models of oxycodone administration are sufficient to elevate global withdrawal scores, but, when compared with oral consumption, s.c. oxycodone injections yielded more pronounced effects on some withdrawal-like behaviors.

处方类阿片(如羟考酮)的过度处方和滥用在很大程度上导致了当前的阿片类药物危机。虽然人类通常口服羟考酮,但肠道外给药途径主要用于羟考酮依赖性的临床前模型。为了解决这个问题,最近的研究使用口服自我给药程序来研究啮齿类动物对羟考酮的寻求和戒断。然而,口服羟考酮与肠外注射羟考酮后的行为差异仍不清楚。因此,本研究的目的是利用已建立的阿片类药物依赖模型,比较雌雄小鼠在家庭笼中口服羟考酮(0.5 毫克/毫升)或反复皮下注射羟考酮(10 毫克/千克)后的焦虑和戒断行为。在这里,小鼠接受了为期 10 天的口服或皮下注射羟考酮治疗,在强迫戒断 72 小时后,使用高架零迷宫、空旷场地和纳洛酮诱导的沉淀戒断程序测量了焦虑和戒断样行为。口服和静脉注射羟考酮后,总体戒断评分的增加程度相似,而两种羟考酮给药途径对焦虑样行为的影响都很小。与口服羟考酮的小鼠相比,静脉注射羟考酮的小鼠在纳洛酮诱导的沉淀性戒断过程中表现出更多的爪颤和跳跃。这些结果表明,两种羟考酮给药模式都足以提高总体戒断评分,但与口服相比,静脉注射羟考酮对某些戒断样行为的影响更为明显。
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引用次数: 0
D2-like dopamine receptors blockade within the dentate gyrus shows a greater effect on stress-induced analgesia in the tail-flick test compared to D1-like dopamine receptors. 与 D1 类多巴胺受体相比,阻断齿状回内的 D2 类多巴胺受体对尾舔试验中应激诱导的镇痛效果更大。
IF 1.6 4区 心理学 Q3 BEHAVIORAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-06-11 DOI: 10.1097/FBP.0000000000000782
Homayoon Golmohammadi, Diba Shirmohammadi, Sajad Mazaheri, Abbas Haghparast

Introduction: Acute stress, as a protective mechanism to respond to an aversive stimulus, can often be accompanied by suppressing pain perception via promoting consistent burst firing of dopamine neurons. Besides, sensitive and advanced research techniques led to the recognition of the mesohippocampal dopaminergic terminals, particularly in the hippocampal dentate gyrus (DG). Moreover, previous studies have shown that dopamine receptors within the hippocampal DG play a critical role in induced antinociceptive responses by forced swim stress (FSS) in the presence of inflammatory pain. Since different pain states can trigger various mechanisms and transmitter systems, the present experiments aimed to investigate whether dopaminergic receptors within the DG have the same role in the presence of acute thermal pain.

Methods: Ninety-seven adult male albino Wistar rats underwent stereotaxic surgery, and a stainless steel guide cannula was unilaterally implanted 1 mm above the DG. Different doses of SCH23390 or sulpiride as D1- and D2-like dopamine receptor antagonists were microinjected into the DG 5-10 min before exposure to FSS, and 5 min after FSS exposure, the tail-flick test evaluated the effect of stress on the nociceptive response at the time-set intervals.

Results: The results demonstrated that exposure to FSS could significantly increase the acute pain perception threshold, while intra-DG administration of SCH23390 and sulpiride reduced the antinociceptive effect of FSS in the tail-flick test.

Discussion: Additionally, it seems the D2-like dopamine receptor within the DG plays a more prominent role in FSS-induced analgesia in the acute pain model.

导言急性应激作为对厌恶刺激做出反应的一种保护机制,通常会通过促进多巴胺神经元的持续爆发性发射来抑制痛觉。此外,灵敏而先进的研究技术还发现了中海马多巴胺能终端,尤其是海马齿状回(DG)中的多巴胺能终端。此外,先前的研究表明,在炎性疼痛的情况下,海马齿状回内的多巴胺受体在强迫游泳应激(FSS)诱导的抗痛觉反应中起着关键作用。由于不同的疼痛状态可触发不同的机制和递质系统,本实验旨在研究海马DG内的多巴胺能受体在急性热痛中是否具有相同的作用:方法:97只成年雄性白化Wistar大鼠接受立体定向手术,在DG上方1毫米处单侧植入不锈钢导管。在暴露于FSS前5-10分钟向DG微量注射不同剂量的D1-和D2-样多巴胺受体拮抗剂SCH23390或舒必利,暴露于FSS后5分钟,在设定的时间间隔内进行尾搔试验,评估应激对痛觉反应的影响:结果表明,暴露于FSS可显著提高急性痛觉阈值,而在DG内给予SCH23390和舒必利可降低FSS在尾叩试验中的抗痛觉效应:此外,在急性疼痛模型中,DG内的D2样多巴胺受体似乎在FSS诱导的镇痛中起着更重要的作用。
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引用次数: 0
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Behavioural Pharmacology
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