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Substitutability of nicotine and sucrose in rats: A behavioral economic analysis 尼古丁和蔗糖在大鼠体内的可替代性:一项行为经济学分析。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-14 DOI: 10.1016/j.pbb.2023.173635
Patricia E. Bunney , John R. Smethells , Mark G. LeSage

Despite considerable evidence suggesting that sweet foods are a substitute for nicotine in humans, no formal behavioral economic analysis of this interrelationship has been conducted in nonhumans. The purpose of the present study was to examine this phenomenon in rats using concurrent schedules of sucrose pellet, chow pellet, and nicotine reinforcer delivery. Rats responded on separate levers that delivered sucrose pellets, chow pellets, or nicotine infusions under concurrent fixed-ratio (FR) 1 schedules for each commodity within a closed economy. Following stable food and nicotine intake, the unit price of either sucrose or nicotine (the primary commodity) was increased while the two alternative commodities remained unchanged. Substitution was quantified using a behavioral economic cross-price model, as well as a novel commodity relation index that normalizes consumption of dissimilar commodities. Asymmetrical partial substitution was observed, wherein sucrose served as a partial substitute for nicotine, but nicotine failed to substitute for sucrose. Moreover, sucrose was a stronger partial substitute for nicotine than chow in most rats. These findings indicate that substitution of food for nicotine depends on the type of food. These findings mirror the selective increase in carbohydrate intake that can occur during smoking cessation and demonstrate a behavioral economic mechanism that may mediate it.

尽管有相当多的证据表明甜食可以替代人类的尼古丁,但尚未对非人类的这种相互关系进行正式的行为经济学分析。本研究的目的是在大鼠中使用蔗糖颗粒、食物颗粒和尼古丁增强剂的同时给药来检测这种现象。在封闭经济中,大鼠对每种商品在同时固定比率(FR)1的时间表下递送蔗糖颗粒、食物颗粒或尼古丁输注的单独杠杆做出反应。在食物和尼古丁摄入量稳定后,蔗糖或尼古丁(主要商品)的单价有所上涨,而这两种替代商品保持不变。使用行为经济交叉价格模型以及一种新的商品关系指数对替代进行量化,该指数使不同商品的消费正常化。观察到不对称部分取代,其中蔗糖作为尼古丁的部分替代品,但尼古丁不能替代蔗糖。此外,在大多数大鼠中,蔗糖比食物更能部分替代尼古丁。这些发现表明,食物对尼古丁的替代取决于食物的类型。这些发现反映了戒烟期间碳水化合物摄入的选择性增加,并证明了一种可能介导这种情况的行为经济机制。
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引用次数: 0
A systematic review of cannabidiol trials in neurodevelopmental disorders 大麻二酚治疗神经发育障碍的系统综述。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-01 DOI: 10.1016/j.pbb.2023.173607
Nina-Francecsa Parrella , Aron Thomas Hill , Peter Gregory Enticott , Pamela Barhoun , Isabella Simone Bower , Talitha Caitlyn Ford

Cannabis-derived compounds, such as cannabidiol (CBD) and delta-9-trans-tetrahydrocannabinol (THC), are increasingly prescribed for a range of clinical indications. These phyto-cannabinoids have multiple biological targets, including the body's endocannabinoid system. There is growing scientific interest in the use of CBD, a non-intoxicating compound, to ameliorate symptoms associated with neurodevelopmental disorders. However, its suitability as a pharmaceutical intervention has not been reliably established in these clinical populations.

This systematic review examines the nine published randomised controlled trials (RCTs) that have probed the safety and efficacy of CBD in individuals diagnosed with attention deficit hyperactivity disorder, autism spectrum disorder, intellectual disability, Tourette Syndrome, and complex motor disorders. Studies were identified systematically through searching four databases: Medline, CINAHL complete, PsycINFO, and EMBASE.

Inclusion criteria were randomised controlled trials involving CBD and participants with neurodevelopmental disorders. No publication year or language restrictions were applied. Relevant data were extracted from the identified list of eligible articles. After extraction, data were cross-checked between the authors to ensure consistency.

Several trials indicate potential efficacy, although this possibility is currently too inconsistent across RCTs to confidently guide clinical usage. Study characteristics, treatment properties, and outcomes varied greatly across the included trials. The material lack of comparable RCTs leaves CBD's suitability as a pharmacological treatment for neurodevelopmental disorders largely undetermined. A stronger evidence base is urgently required to establish safety and efficacy profiles and guide the ever-expanding clinical uptake of cannabis-derived compounds in neurodevelopmental disorders.

Prospero registration number: CRD42021267839.

大麻衍生化合物,如大麻二酚(CBD)和δ-9-反式四氢大麻酚(THC),越来越多地被用于一系列临床适应症。这些植物大麻素具有多种生物靶标,包括人体的内源性大麻素系统。CBD是一种非致醉化合物,用于改善与神经发育障碍相关的症状,科学界对此越来越感兴趣。然而,它作为药物干预的适用性尚未在这些临床人群中得到可靠的证实。这篇系统综述考察了九项已发表的随机对照试验(RCT),这些试验探讨了CBD在被诊断为注意力缺陷多动障碍、自闭症谱系障碍、智力残疾、抽动秽语综合征和复杂运动障碍的个体中的安全性和有效性。通过检索Medline、CINAHL complete、PsycINFO和EMBASE四个数据库,系统地确定了研究。纳入标准为随机对照试验,涉及CBD和患有神经发育障碍的参与者。没有出版年份或语言限制。相关数据是从已确定的合格文章列表中提取的。提取后,对作者之间的数据进行交叉检查,以确保一致性。几项试验表明了潜在的疗效,尽管目前随机对照试验中这种可能性太不一致,无法自信地指导临床使用。研究特征、治疗特性和结果在纳入的试验中差异很大。由于缺乏可比的随机对照试验,CBD作为神经发育障碍药物治疗的适用性在很大程度上尚未确定。迫切需要更强有力的证据基础来建立安全性和有效性档案,并指导大麻衍生化合物在神经发育障碍中不断扩大的临床摄取。Prospero注册号:CRD42021267839。
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引用次数: 2
Emotional behaviors as well as the hippocampal reelin expression in C57BL/6N male mice chronically treated with corticosterone 慢性皮质酮治疗的C57BL/6N雄性小鼠的情绪行为和海马reelin表达。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-01 DOI: 10.1016/j.pbb.2023.173617
Daisuke Ibi , Genki Nakasai , Masahito Sawahata , Rika Takaba , Maho Kinoshita , Kiyofumi Yamada , Masayuki Hiramatsu

Depression is a common psychiatric disorder affecting around 300 million people worldwide. Serum cortisol and glucocorticoid levels in humans are reportedly higher in patients with depression compared to controls. Furthermore, rodents repeatedly treated with exogenous corticosterone (CORT), a glucocorticoid in rodents, exhibit deficits in emotional behaviors. To confirm the availability of mice with chronic CORT treatment as an animal model of depression, we investigated the effect of chronic CORT treatment on depression-like behavioral and neuropathological phenotypes in C57BL/6N male mice. Behavioral studies showed depression- and anxiety-like behaviors in mice treated with CORT compared with control mice in the forced-swim and elevated-plus maze tests. Additionally, treated mice represented anhedonia and social behavior impairments in the sucrose preference and social interaction tests, respectively. Brains of depression patients have altered expression of reelin, an extracellular matrix protein involved in neuronal development and function. Likewise, in the present study, mice with chronic CORT treatment also exhibited reelin downregulation in cells of the hippocampus. Hence, we investigated therapeutic effects of reelin supplementation on CORT-induced behavioral abnormalities in mice. Microinjections of recombinant reelin protein into the hippocampus did not rescue behavioral deficits in mice with chronic CORT treatment. These results suggest that C57BL/6N male mice chronically treated with CORT are a suitable animal depression model, in which depressive behaviors may occur independently of the alternation of hippocampal Reelin expression.

抑郁症是一种常见的精神疾病,影响着全世界约3亿人。据报道,抑郁症患者的血清皮质醇和糖皮质激素水平高于对照组。此外,反复使用外源性皮质酮(CORT)(啮齿类动物的一种糖皮质激素)治疗的啮齿类动物表现出情绪行为缺陷。为了证实慢性CORT治疗小鼠作为抑郁症动物模型的可用性,我们研究了慢性CORT处理对C57BL/6N雄性小鼠抑郁样行为和神经病理学表型的影响。行为研究显示,在强迫游泳和提升+迷宫测试中,与对照小鼠相比,接受CORT治疗的小鼠表现出抑郁和焦虑样行为。此外,在蔗糖偏好和社会互动测试中,接受治疗的小鼠分别表现出快感缺乏和社会行为障碍。抑郁症患者的大脑改变了reelin的表达,reelin是一种参与神经元发育和功能的细胞外基质蛋白。同样,在本研究中,接受慢性CORT治疗的小鼠海马细胞中也表现出reelin下调。因此,我们研究了补充reelin对CORT诱导的小鼠行为异常的治疗作用。在接受慢性CORT治疗的小鼠中,向海马微量注射重组reelin蛋白并不能挽救其行为缺陷。这些结果表明,长期用CORT治疗的C57BL/6N雄性小鼠是一种合适的动物抑郁模型,其中抑郁行为可能独立于海马Reelin表达的改变而发生。
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引用次数: 0
Stimulation of lateral parabrachial (LPB) to central amygdala (CeA) pituitary adenylate cyclase-activating polypeptide (PACAP) neurons induces anxiety-like behavior and mechanical allodynia 臂旁外侧(LPB)对中央杏仁核(CeA)、垂体腺苷酸环化酶激活多肽(PACAP)神经元的刺激可诱导焦虑样行为和机械性异常性疼痛。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-01 DOI: 10.1016/j.pbb.2023.173605
Mariel P. Seiglie , Lauren Lepeak , Sophia Miracle, Pietro Cottone, Valentina Sabino

Background

Anxiety disorders are the most prevalent psychiatric disorders, and they are highly comorbid with chronic pain conditions. The central nucleus of the amygdala (CeA) is known not only for its role in the regulation of anxiety but also as an important site for the negative affective dimension of pain. Pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide whose terminals are abundant in the CeA, is strongly implicated in the stress response as well as in pain processing. Here, using Cre-dependent viral vectors, we explored in greater detail the role of the PACAP projection to the CeA that originates in the lateral parabrachial nucleus (LPB).

Methods

We first performed a circuit mapping experiment by injecting an anterograde Cre-dependent virus expressing a fluorescent reporter in the LPB of PACAP-Cre mice and observing their projections. Then, we used a chemogenetic approach (a Cre-dependent Designer Receptors Activated by Designer Drugs, DREADDs) to assess the effects of the direct stimulation of the PACAP LPB to CeA projection on general locomotor activity, anxiety-like behavior (using a defensive withdrawal test), and mechanical pain sensitivity (using the von Frey test).

Results

We found that the CeA, together with other areas, is one of the major downstream projection targets of PACAP neurons originating in the lateral parabrachial nucleus (LPB). In the DREADD experiment, we then found that the selective activation of this neuronal pathway is sufficient to increase both anxiety-like behavior and mechanical pain sensitivity in mice, without affecting general locomotor activity.

Conclusion

In conclusion, our data suggest that the dysregulation of this circuit may contribute to a variety of anxiety disorders and chronic pain states, and that PACAP may represent an important therapeutic target for the treatment of these conditions.

背景:焦虑症是最常见的精神疾病,与慢性疼痛有高度的共病性。杏仁核中央核(CeA)不仅因其在焦虑调节中的作用而闻名,而且也是疼痛负面情感维度的重要部位。垂体腺苷酸环化酶激活多肽(PACAP)是一种末端在CeA中丰富的神经肽,与应激反应和疼痛处理密切相关。在这里,使用Cre依赖性病毒载体,我们更详细地探索了PACAP向源自臂旁外侧核(LPB)的CeA的投射的作用。然后,我们使用化学遗传学方法(一种由设计药物激活的Cre依赖性设计受体,DREADDs)来评估PACAP LPB对CeA投射的直接刺激对一般运动活动、焦虑样行为(使用防御性戒断测试)和机械疼痛敏感性(使用von Frey测试)的影响。结果:我们发现,其与其他区域一起是起源于臂旁外侧核(LPB)的PACAP神经元的主要下游投射靶点之一。在DREADD实验中,我们发现这种神经元通路的选择性激活足以增加小鼠的焦虑样行为和机械疼痛敏感性,而不会影响一般的运动活动。结论:总之,我们的数据表明,该回路的失调可能导致各种焦虑症和慢性疼痛状态,PACAP可能是治疗这些疾病的重要治疗靶点。
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引用次数: 0
Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice 在雄性和雌性C57BL/6J小鼠的强迫游泳试验中,雷替加宾促进氯胺酮的抗抑郁作用。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-01 DOI: 10.1016/j.pbb.2023.173590
Yixue Qin , Haoxuan Li , Yuqi Zhang , Jun-Li Cao , Wenxin Zhang , Hongxing Zhang

Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that intraperitoneal injection of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.

氯胺酮在特定的临床环境中越来越多地被用作一种快速起效的抗抑郁药。然而,作为一种迷幻试剂,其潜在的生理和心理依赖性限制了其临床应用。在此,我们在雄性和雌性C57BL/6J小鼠的强迫游泳试验中,添加了一种KCNQ通道开放剂retigabine作为辅助治疗,以观察其对氯胺酮抗抑郁特性的影响。行为数据表明,在强迫游泳试验中,腹膜内注射氯胺酮对动物的不动性能表现出剂量依赖性影响。在用相对较低剂量的氯胺酮治疗的小鼠中,添加雷替加宾足以诱导显著的抗抑郁作用,单独给药时氯胺酮不能起到抗抑郁作用。当同时给予瑞加宾时,氯胺酮在强迫游泳试验中的抗抑郁作用显著增强,有效时间延长。总之,雄性和雌性小鼠的这些结果表明,雷替加宾的辅助治疗是促进氯胺酮抗抑郁作用的一种替代方案,因此有可能遇到其可能的生理和心理依赖。
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引用次数: 0
Chronic exposure of female mice to selective serotonin reuptake inhibitors during lactation induces vocal behavior deficits in pre-weaned offspring 雌性小鼠在哺乳期长期暴露于选择性血清素再摄取抑制剂会导致断奶前后代的发声行为缺陷。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-01 DOI: 10.1016/j.pbb.2023.173606
Ziguo Lan , Ryosuke O. Tachibana , Kouta Kanno

Developmental factors for autism spectrum disorders (ASDs) have been an ongoing debate despite an increasing number of reports on genetic factors. Recent studies have suggested maternal intake of selective serotonin reuptake inhibitors (SSRIs) as a possible developmental factor elevating the risk for ASD in offspring. Here, we show that maternal exposure of mice to an SSRI, Fluoxetine (FLX), induces abnormal ultrasonic vocalizations (USVs), an indicator of ASD-related behavior. We tested the effect of FLX intake during pregnancy, lactation, or both. We found that the lactation and both conditions decreased the number of USVs emitted by offspring pups. An index for assessing the syllables' frequency modulation revealed that highly modulated syllables appeared to be inhibited only in both conditions. Furthermore, we found that the number of serotonergic neurons at adulthood was reduced in the progeny of mice treated with FLX in all conditions. In addition, maternal exposure to FLX through pregnancy and lactation induced a high death rate of early post-natal pups. These suggest that the maternal exposure to SSRIs affects early development of offsprings as well as the serotonergic system. Focusing on vocal communication, our results indicate that intake of an SSRI during lactation increases the risk of abnormal USVs in pups, and provides potential insights into the development of ASD.

尽管关于遗传因素的报道越来越多,但自闭症谱系障碍(ASD)的发育因素一直是一个持续的争论。最近的研究表明,母体摄入选择性血清素再摄取抑制剂(SSRIs)可能是提高后代ASD风险的一个发育因素。在这里,我们发现,母体暴露于氟西汀(FLX)SSRI的小鼠会诱导异常超声发声(USVs),这是ASD相关行为的指标。我们测试了在妊娠期、哺乳期或两者同时服用FLX的效果。我们发现,哺乳期和这两种情况都降低了幼崽发出的USVs的数量。评估音节频率调制的指数显示,高度调制的音节似乎只有在这两种情况下才会被抑制。此外,我们发现,在所有条件下,用FLX处理的小鼠的后代在成年时5-羟色胺能神经元的数量都减少了。此外,母亲在怀孕和哺乳期间接触FLX会导致产后早期幼崽的高死亡率。这些表明,母体暴露于SSRIs会影响后代的早期发育以及血清素能系统。专注于声音交流,我们的研究结果表明,哺乳期摄入SSRI会增加幼崽发生异常USV的风险,并为ASD的发展提供了潜在的见解。
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引用次数: 0
Opiophobia and the tragedy of needless pain: A call for education and balance 鸦片恐惧症和无谓痛苦的悲剧:呼吁教育和平衡。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-01 DOI: 10.1016/j.pbb.2023.173616
Keith A. Trujillo
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引用次数: 0
Atomoxetine promotes incentive value of modafinil and sensitizes exploratory behavior 阿托莫西汀促进莫达非尼的激励价值,并提高探索行为的敏感性。
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-09-01 DOI: 10.1016/j.pbb.2023.173618
Jesús E. Yepez, Jorge Juárez

Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of psychostimulants is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the dopaminergic system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male Wistar rats at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances –60MOD + 2ATX and 60MOD + 4ATX– or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixture. In addition, the 60MOD, 2ATX, and 60MOD + 2ATX groups showed sensitization of exploratory behavior after ingesting the mixture. Results suggest that the noradrenergic system enhances the incentive value of MOD and a MOD+ATX mixture, while also playing an important role in the sensitization of exploratory behavior.

物质依赖是一种由于频繁滥用药物而改变神经系统功能的疾病。多巴胺在精神刺激剂成瘾作用中的作用是众所周知的;然而,去甲肾上腺素能系统的参与仍不清楚,也不太清楚,尽管已知可卡因和安非他命等药物对该系统具有显著的活性。药物莫达非尼(MOD)没有被证实的成瘾作用。它主要作用于多巴胺能系统,在较小程度上作用于去甲肾上腺素(NOR)系统,从而促进清醒。阿托莫西汀(ATX)是一种非刺激性药物,只作用于NOR系统,增强其活性。本研究的目的是分析共同激活DA和NOR系统(分别与MOD和ATX)对运动活动和探索行为的影响,并检验MOD和MOD+ATX混合物可能出现的奖励特性。雄性Wistar大鼠在出生后第60天用2ATX、4ATX或60MOD mg/kg、这些物质的两种组合(60MOD+2ATX和60MOD+4ATX)或载体进行慢性治疗(16天)。与60MOD+4ATX共同给药的大鼠降低了MOD诱导的饲养行为频率,但这种行为在慢性治疗后通过自行给药MOD+ATX混合物而致敏。用60MOD+4ATX预处理的大鼠显示出更高的MOD自给药和更大的获得MOD+ATX混合物的操作任务活性。此外,60MOD、2ATX和60MOD+2ATX组在摄入混合物后表现出探索行为的敏感性。结果表明,去甲肾上腺素能系统提高了MOD和MOD+ATX混合物的激励值,同时在探索行为的敏化中也发挥了重要作用。
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引用次数: 0
Theophylline reverses oxycodone's but not fentanyl's respiratory depression in mice while caffeine is ineffective against both opioids 茶碱能逆转羟考酮对小鼠的呼吸抑制作用,但不能逆转芬太尼的作用,而咖啡因对这两种阿片类药物都无效
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-08-01 DOI: 10.1016/j.pbb.2023.173601
Harrison J. Elder , D. Matthew Walentiny , Patrick M. Beardsley

Rationale

The opioid epidemic remains a pressing public health crisis in the United States. Most of these overdose deaths are a result of lethal respiratory depression. In recent years the increasing incidence of opioid-involved overdose deaths has been driven by fentanyl, which is more resistant to adequate reversal by naloxone (NARCAN ®) than semi-synthetic or classical morphinan predecessors like oxycodone and heroin. For this and other reasons (e.g., precipitating withdrawal) non-opioidergic pharmacotherapies to reverse opioid-depressed respiration are needed. Methylxanthines are a class of stimulant drugs including caffeine and theophylline which exert their effects primarily via adenosine receptor antagonism. Evidence suggests methylxanthines can stimulate respiration by enhancing neural activity in respiratory nuclei in the pons and medulla independent of opioid receptors. This study aimed to determine whether caffeine and theophylline can stimulate respiration in mice when depressed by fentanyl and oxycodone.

Methods

Whole-body plethysmography was used to characterize fentanyl and oxycodone's effects on respiration and their reversal by naloxone in male Swiss Webster mice. Next, caffeine and theophylline were tested for their effects on basal respiration. Finally, each methylxanthine was evaluated for its ability to reverse similar levels of respiratory depression induced by fentanyl or oxycodone.

Results and conclusions

Oxycodone and fentanyl dose-dependently reduced respiratory minute volume (ml/min; MVb) that was reversible by naloxone. Caffeine and theophylline each significantly increased basal MVb. Theophylline, but not caffeine, completely reversed oxycodone-depressed respiration. In contrast, neither methylxanthine elevated fentanyl-depressed respiration at the doses tested. Despite their limited efficacy for reversing opioid-depressed respiration when administered alone, the methylxanthines safety, duration, and mechanism of action supports further evaluation in combination with naloxone to augment its reversal of opioid-depressed respiration.

阿片类药物的流行在美国仍然是一个紧迫的公共卫生危机。这些过量死亡大多是致命的呼吸抑制造成的。近年来,与羟考酮和海洛因等半合成或经典吗啡酮相比,芬太尼对纳洛酮(NARCAN®)的充分逆转更具抗性,导致阿片类药物过量死亡的发生率不断上升。由于这个原因和其他原因(例如,急性戒断),需要非阿片类药物治疗来逆转阿片类药物抑制的呼吸。甲基黄嘌呤是一类兴奋剂,包括咖啡因和茶碱,主要通过腺苷受体拮抗剂发挥作用。有证据表明,甲基黄嘌呤可以通过增强脑桥和髓质的呼吸核的神经活动来刺激呼吸,而不依赖于阿片受体。这项研究旨在确定咖啡因和茶碱是否能刺激芬太尼和羟考酮抑制小鼠的呼吸。方法采用全身容积脉搏波法观察芬太尼和羟考酮对雄性瑞士韦氏小鼠呼吸的影响及纳洛酮对呼吸的逆转作用。接下来,研究人员测试了咖啡因和茶碱对基础呼吸的影响。最后,评估每种甲基黄嘌呤逆转芬太尼或羟考酮引起的类似水平呼吸抑制的能力。结果与结论羟考酮和芬太尼剂量依赖性降低呼吸分气量(ml/min;MVb)可被纳洛酮逆转。咖啡因和茶碱均显著增加基础MVb。茶碱,而不是咖啡因,完全逆转了氧可酮抑制的呼吸。相比之下,在测试的剂量下,甲基黄嘌呤都没有增加芬太尼抑制的呼吸。尽管单独使用甲基黄嘌呤逆转阿片类药物抑制呼吸的效果有限,但其安全性、持续时间和作用机制支持进一步评估与纳洛酮联合使用以增强其逆转阿片类药物抑制呼吸的作用。
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引用次数: 0
Neuroprotective effects of novel pyrrolidine-2-one derivatives on scopolamine-induced cognitive impairment in mice: Behavioral and biochemical analysis 新型吡咯烷-2- 1衍生物对东莨菪碱诱导的小鼠认知障碍的神经保护作用:行为和生化分析
IF 3.6 3区 心理学 Q1 BEHAVIORAL SCIENCES Pub Date : 2023-08-01 DOI: 10.1016/j.pbb.2023.173602
Swati Pant, Mohan Gupta, Tulika Anthwal, Monika Chauhan, Sumitra Nain

Alzheimer's disease (AD) is a long-term neurodegenerative condition that impairs cognitive abilities. In brain acetylcholine deficit and oxidative stress may be considered the key pathogenic causes for AD, even though the basic etiology is still unknown. The effects of some novel pyrrolidine-2-one derivatives on the learning and memory deficits caused by scopolamine in mice were examined in the current study. The learning and memory parameters were assessed using the morris water maze test, rota rod test the and locomotor activity. A number of biochemical factors were also evaluated, including acetylcholinesterase (AChE), lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CA), and nitrite oxide (NO) assay. The current study shows that these derivatives were more effective and comparable to donepezil at treating the behavioral and biochemical changes brought on by scopolamine. The observed results showed pyrrolidine-2-one derivatives as a promising candidate for diseases associated with cognitive deficits.

阿尔茨海默病(AD)是一种长期的神经退行性疾病,会损害认知能力。脑内乙酰胆碱缺乏和氧化应激可能被认为是AD的主要致病原因,尽管其基本病因尚不清楚。本文研究了几种新型吡咯烷-2- 1衍生物对东莨菪碱所致小鼠学习记忆障碍的影响。采用morris水迷宫测试、旋转棒测试和运动能力测试评估学习记忆参数。许多生化因素也被评估,包括乙酰胆碱酯酶(AChE)、脂质过氧化(LPO)、还原性谷胱甘肽(GSH)、超氧化物歧化酶(SOD)、过氧化氢酶(CA)和亚硝酸盐氧化物(NO)测定。目前的研究表明,这些衍生物在治疗东莨菪碱引起的行为和生化变化方面比多奈哌齐更有效。观察到的结果表明吡咯烷-2- 1衍生物是认知缺陷相关疾病的有希望的候选者。
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Pharmacology Biochemistry and Behavior
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