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Training Experimentally Naive Harbor Seals to Participate in Vocal Learning Experiments in a Zoo 在动物园训练对实验一无所知的海豹参与发声学习实验
Pub Date : 2024-09-13 DOI: 10.1101/2024.08.27.609954
Diandra Duengen, Andrea Ravignani
Harbor seals (Phoca vitulina) are a common zoo species that show a scientifically valuable propensity for vocal learning. Under human care, the seals can be trained to associate vocalizations with cues. This ability is termed vocal usage learning and is characterized by learning to use a vocalization in a specific context. Among mammals, seals are prime candidates to investigate vocal learning. Yet, only a handful of reports exist on harbor seal vocal learning abilities and even less document how these were trained or tested. Here, we investigate how, and if, two experimentally naive harbor seals under human care, can be trained to participate in scientific experiments. We describe the training and testing of two seals in two basic vocal learning experiments. We trained the animals to vocalize upon the presentation of discriminative stimuli (SD) through operant conditioning methods and tested their abilities to i) vocalize and refrain from vocalizing on two distinct SDs, and ii) produce two different vocalizations upon the presentation of two different SDs. Both seals learned the tasks: the first task was achieved within 118 trials (22 errors to criterion) and 220 trials (40 errors to criterion), the second task within 480 trials (158 errors to criterion) and 380 trials (94 errors to criterion), respectively. Our results confirm that harbor seals are capable of vocal usage learning and further suggest that associating individually distinct vocalizations with different SDs may be more cognitively demanding than vocalizing and being silent on SD.
港海豹(Phoca vitulina)是动物园中常见的物种,它的发声学习倾向在科学上很有价值。在人类的照料下,可以训练海豹将发声与提示联系起来。这种能力被称为 "发声使用学习",其特点是学会在特定环境中使用一种发声方式。在哺乳动物中,海豹是研究发声学习的主要对象。然而,关于港海豹发声学习能力的报道寥寥无几,而关于如何训练或测试这种能力的记录更是少之又少。在这里,我们研究了如何以及是否可以训练两只在人类照料下的实验幼稚的港海豹参与科学实验。我们描述了两只海豹在两个基本发声学习实验中的训练和测试情况。我们通过操作性条件反射方法训练海豹在辨别性刺激(SD)出现时发声,并测试它们 i) 在两种不同的 SD 出现时发声和不发声的能力,以及 ii) 在两种不同的 SD 出现时发出两种不同声音的能力。两只海豹都学会了这些任务:第一项任务分别在 118 次试验(22 次误差为标准)和 220 次试验(40 次误差为标准)内完成,第二项任务分别在 480 次试验(158 次误差为标准)和 380 次试验(94 次误差为标准)内完成。我们的研究结果证实,海豹有能力学习发声用法,并进一步表明,将不同的发声与不同的SD联系起来可能比在SD上发声和保持沉默对认知的要求更高。
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引用次数: 0
Rapamycin alters the feeding preference for amino acids and sugar in female Drosophila 雷帕霉素改变了雌果蝇对氨基酸和糖的摄食偏好
Pub Date : 2024-09-12 DOI: 10.1101/2024.09.10.611925
Guixiang Yu, Qihao Yang, Qi Wu
Pharmacological interventions targeting the aging process hold significant promise for improving the quality of life in the elderly and reducing healthcare costs. Rapamycin, in particular, has exhibited significant anti-aging and lifespan-extending effects across multiple model organisms. However, chronic rapamycin administration may also lead to various adverse reactions since it reshapes energy metabolism. Here, using Drosophila melanogaster as a model, we show that life-prolonging doses of rapamycin significantly modify animal feeding behavior. Long-term administration of rapamycin decreased protein preference in females while enhancing their sugar intake. Utilizing a chemically defined diet, we identified that changes in amino acid and sugar feeding preferences emerged as early as the second day of rapamycin treatment, preceding any detectable decline in fecundity. However, rapamycin-induced changes in macronutrient feeding preferences were not observed in males and sterile mutant females. Overall, our study suggests that the modification of feeding behavior could be a non-negligible side effect of rapamycin treatment, which is influenced by both sex and reproductive status.
针对衰老过程的药物干预对提高老年人的生活质量和降低医疗成本大有可为。特别是雷帕霉素,它在多种模式生物中都表现出了显著的抗衰老和延长寿命的作用。然而,由于雷帕霉素重塑了能量代谢,长期服用雷帕霉素也可能导致各种不良反应。在这里,我们以黑腹果蝇为模型,证明了延长生命剂量的雷帕霉素会显著改变动物的摄食行为。长期服用雷帕霉素会降低雌性果蝇对蛋白质的偏好,同时提高它们的糖摄入量。利用化学定义的饮食,我们发现早在雷帕霉素治疗的第二天,氨基酸和糖的摄食偏好就出现了变化,这比任何可检测到的繁殖力下降都要早。然而,在雄性和不育突变体雌性中没有观察到雷帕霉素诱导的宏量营养素摄食偏好的变化。总之,我们的研究表明,摄食行为的改变可能是雷帕霉素治疗的一个不可忽视的副作用,它同时受到性别和生殖状态的影响。
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引用次数: 0
High early lactational synchrony within baboon groups predicts increased infant mortality 狒狒群体内早期哺乳同步性高可预测婴儿死亡率上升
Pub Date : 2024-09-11 DOI: 10.1101/2024.09.09.611196
Jack C. Winans, Niki H. Learn, I. Long'ida Siodi, J. Kinyua Warutere, Elizabeth A. Archie, Jenny Tung, Susan C. Alberts, A. Catherine Markham
Social group composition can have fitness implications for group members by determining opportunities for affiliative and competitive interactions. Female-female competition may be particularly acute when many groupmates have young infants at the same time, with potential consequences for infant survival. Here, we used decades of data on wild baboons (Papio sp.) in Amboseli, Kenya, to examine the effects of "early lactational synchrony" (here, the proportion of females in a group with an infant <90 days old) on female-female agonistic interactions and infant survival. Because early lactation is an energetically demanding time for mothers and a risky time for infants, we expected early lactational synchrony to produce intensified competition for food and/or male protectors, resulting in more frequent female-female agonistic interactions and high infant mortality. In support of these predictions, we found that the frequency of female-female agonistic interactions increased with increasing early lactational synchrony. Reproductive state affected this relationship: while females in all states (cycling, pregnant, and postpartum amenorrhea) initiated more agonistic interactions when early lactational synchrony was high, only females in postpartum amenorrhea (including, but not limited to, females in early lactation) received more agonistic interactions. Furthermore, while high early lactational synchrony was rare, it strongly predicted infant mortality. This association may result from both aggression among adult females and infanticidal behavior by peripubertal females. These findings provide novel evidence that social dynamics may shape reproductive phenology in a nonseasonal breeder. Specifically, both competition among reproductive females and harassment from nonreproductive females may select against synchronous reproduction.
社会群体的组成可以决定隶属和竞争性互动的机会,从而对群体成员的健康产生影响。当许多群友同时有幼仔时,雌性之间的竞争可能会特别激烈,从而对幼仔的存活造成潜在影响。在这里,我们利用数十年来对肯尼亚安博塞利野生狒狒(Papio sp.)的数据,研究了 "早期哺乳同步性"(这里指群体中婴儿出生 90 天的雌性比例)对雌-雌性激动互动和婴儿存活的影响。由于哺乳早期对母亲来说是能量消耗大的时期,而对婴儿来说则是风险高的时期,因此我们预计哺乳早期同步会加剧对食物和/或雄性保护者的竞争,从而导致更频繁的雌-雌激动互动和更高的婴儿死亡率。为了支持这些预测,我们发现雌性与雌性之间的激动互动频率随着哺乳期早期同步性的增加而增加。生殖状态会影响这种关系:当早期泌乳同步性高时,处于所有状态(周期、怀孕和产后闭经)的雌性都会发起更多的激动互动,但只有产后闭经的雌性(包括但不限于早期泌乳的雌性)才会获得更多的激动互动。此外,虽然早期泌乳同步性高的情况很少见,但它却能强烈预测婴儿死亡率。这种关联可能是成年雌性的攻击行为和围青春期雌性的杀婴行为造成的。这些发现提供了新的证据,证明社会动态可能会影响非季节性繁殖动物的生殖物候学。具体来说,繁殖期雌性之间的竞争和非繁殖期雌性的骚扰可能会阻碍同步繁殖。
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引用次数: 0
Intranasal dantrolene nanoparticles inhibit lipopolysaccharide-induced depression and anxiety behavior in mice 鼻内注射丹曲林纳米颗粒可抑制脂多糖诱发的小鼠抑郁和焦虑行为
Pub Date : 2024-09-11 DOI: 10.1101/2024.09.06.611461
Jia Liu, Yan Lu, Piplu Bhuiyan, Jacob Gruttner, Lauren St. Louis, Yutong Yi, Ge Liang, Huafeng Wei
This study investigates the therapeutic effectiveness of intranasal dantrolene nanoparticles in the Ryanodex formulation (DNRF) pretreatment to inhibit lipopolysaccharide (LPS)-induced depressive and anxiety behavior in mice.Both wild-type (WT) B6SJLF1/J and 5XFAD adult mice were pretreated with intranasal DNRF (5mg/kg), daily, Monday to Friday, 5 days per week, for 4 weeks. Then, mice were treated with intraperitoneal injection of LPS (5mg/kg) for one time. Behavioral tests for depression and anxiety were performed 24 hours after a one-time LPS injection. Biomarkers for inflammation (IL-1β and IL-18) in blood were measured using enzyme-linked immunosorbent assay (ELISA). In both types of mice, intranasal DNRF significantly inhibited LPS-induced pathological elevation of IL-1β and IL-18 in the blood. Intranasal DNRF abolished LPS-induced depression and anxiety behaviors behavior in both WT and 5XFAD mice, without obvious side effects, which was associated with its significant inhibition of pathological elevation of pyroptosis related cytokines in blood.
野生型(WT)B6SJLF1/J和5XFAD成年小鼠均接受鼻内注射DNRF(5mg/kg)预处理,周一至周五每天一次,每周5天,共4周。然后,小鼠腹腔注射一次 LPS(5 毫克/千克)。一次性注射 LPS 24 小时后,对小鼠进行抑郁和焦虑行为测试。血液中的炎症生物标志物(IL-1β和IL-18)采用酶联免疫吸附试验(ELISA)进行测定。在两种类型的小鼠中,鼻内注射 DNRF 都能显著抑制 LPS 诱导的血液中 IL-1β 和 IL-18 的病理性升高。鼻内注射DNRF可消除LPS诱导的WT和5XFAD小鼠的抑郁和焦虑行为,且无明显副作用,这与DNRF显著抑制血液中热休克相关细胞因子的病理性升高有关。
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引用次数: 0
The personal space and the collective behavior of crowd disasters 人群灾难中的个人空间和集体行为
Pub Date : 2024-09-10 DOI: 10.1101/2024.09.05.611443
Igor Lugo, Martha G. Alatriste-Contreras
The concept of the personal space in crowd dynamics is commonly underestimated. However, the self-awareness of it can prevent and handle risk situations in human crowds. The aim of this study was to explore theoretically the use of the personal space as an interdisciplinary concept and design a computational model based on cellular automata for modeling collective behaviors related to crushing events. We generated transitional rules based on the Shelling's spatial proximity model of segregation. Based on an explorative data analysis and model validation, we found that the dynamics of crowd events showed dependencies between similar or dissimilar individual preferences and their interpersonal distances. These results suggests that crushing events in social gatherings are highly probable and that the initial space between attendees is the key for delaying the presence of crowd disasters.
人群动态中的个人空间概念通常被低估。然而,对个人空间的自我意识可以预防和处理人群中的风险情况。本研究旨在从理论上探讨个人空间这一跨学科概念的应用,并设计一个基于细胞自动机的计算模型,用于模拟与挤压事件相关的集体行为。我们根据 Shelling 的空间邻近性隔离模型生成了过渡规则。在探索性数据分析和模型验证的基础上,我们发现人群事件的动态表现出相似或不相似的个体偏好与他们的人际距离之间的依赖关系。这些结果表明,社交聚会中的挤压事件极有可能发生,而与会者之间的初始空间是延迟人群灾难出现的关键。
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引用次数: 0
Paradise fish (Macropodus opercularis) as novel translational model for emotional and cognitive function 天堂鱼(Macropodus opercularis)作为情绪和认知功能的新型转化模型
Pub Date : 2024-09-10 DOI: 10.1101/2024.09.06.611721
Zoltan K Varga, Diana Pejtsik, Timea Csorvas, Eva Mikics, Adam Miklosi, Mate Varga
Zebrafish have revolutionised physiological screening in vertebrates, but the interpretation of individual-based behavioural assays is burdened by the strong sociality of this species. We propose the use of a solitaire fish species, the paradise fish to keep the advantages and compensate for the limitations of the zebrafish model. We compared juvenile paradise fish and zebrafish in social and non-social exploratory tasks, anxiety tests and in a working memory assay to assess their performance in these individual-based models. We found that in contrast to zebrafish, paradise fish did not show social approach in the U-shape sociability test, their novelty exploration was not biased by the presence of a conspecific in the slalom test, and was not impaired by social isolation in the showjump or in the swimming plus-maze (SPM) anxiety tests. While social circumstances did not affect the anxiety of paradise fish, it was sensitive to the anxiolytic drug buspirone. Intra- and interest repeatability measures of the anxiety tests revealed that paradise fish express more consistent exploratory and defensive behaviours regarding time and context compared to zebrafish. Behavioural consistency in paradise fish was also supported by arm alternation as a predominant choice of exploration in the y-maze task. In summary, our results indicate that the behaviour of paradise fish is less biased by social cues and is more effective and repeatable in individual-based assays than zebrafish behaviour. We hypothesise that the two phenomena are connected and novelty exploration, anxiety and working memory can be more reliably measured and are translatable in a solitaire species.
斑马鱼为脊椎动物的生理筛选带来了革命性的变化,但基于个体的行为分析却因其强烈的社会性而难以解释。我们建议使用单人鱼种--天堂鱼来保持斑马鱼模型的优势并弥补其局限性。我们比较了天堂鱼和斑马鱼幼鱼在社会性和非社会性探索任务、焦虑测试和工作记忆测试中的表现,以评估它们在这些基于个体的模型中的表现。我们发现,与斑马鱼不同的是,天堂鱼在U形交际性测试中不表现出社会接近性,在回旋测试中,它们的新奇探索不会因为同种鱼的存在而受到影响,在表演跳跃和游泳加迷宫(SPM)焦虑测试中,它们也不会因为社会隔离而受到影响。虽然社会环境不会影响天堂鱼的焦虑,但它对抗焦虑药物丁螺环酮很敏感。焦虑测试的内部和兴趣重复性测量显示,与斑马鱼相比,天堂鱼在时间和环境方面表现出更一致的探索和防御行为。天堂鱼的行为一致性也得到了Y迷宫任务中手臂交替作为主要探索选择的支持。总之,我们的研究结果表明,与斑马鱼的行为相比,天堂鱼的行为受社会线索的影响较小,而且在以个体为基础的实验中更有效、更可重复。我们假设这两种现象是相互关联的,而且新奇探索、焦虑和工作记忆可以更可靠地测量,并可在单人鱼种中转化。
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引用次数: 0
Controlled and polygynous mating in the black soldier fly: advancing breeding programs through quantitative genetic designs 黑兵蝇的受控交配和多雌交配:通过定量遗传设计推进育种计划
Pub Date : 2024-09-10 DOI: 10.1101/2024.09.09.611978
Kim Jensen, Sarah Fogh Thormose, Natasja Krog Noer, Toke Munk Schou, Morten Kargo, Anton Gligorescu, Jan Vaerum Noergaard, Laura Skrubbeltrang Hansen, Roos Marina Zaalberg, Hanne Marie Nielsen, Torsten Nygaard Kristensen
In animal breeding programs, utilizing quantitative genetic designs such as the full-/half-sibling design is fundamental. A full-/half-sibling design demands that mating can be controlled, and individuals can be tracked for the construction of a pedigree. In nature, black soldier fly (Hermetia illucens L.) males are reported to gather in lekking groups to engage in competitive displays and courtship rituals before mating. This lekking behavior is described as crucial for establishing suitable conditions and achieving successful mating, and polygyny is therefore assumed to be rare. We show that when exposing a virgin male to a virgin female, they readily mate, demonstrating the ability to mate without prior lekking and that it is possible to mate selected pairs. Furthermore, we show that successful mating can be achieved between an individual male and at least four virgin females within a four-hour time span, and that nearly all matings result in live offspring. Our findings pave the way for moving H. illucens breeding programs beyond mass selection towards advanced selective breeding designs demanding controlled mating. Such designs enable selection for multiple traits simultaneously, are used to prevent inbreeding, and can drastically increase rates of selection responses compared to mass selection.
在动物育种计划中,利用全同胞/半同胞设计等定量遗传设计至关重要。全同胞/半同胞设计要求能控制交配,并能跟踪个体以构建血统。据报道,在自然界中,黑色兵蝇(Hermetia illucens L.)的雄蝇会在交配前聚集成群,进行竞争性表演和求偶仪式。据描述,这种lekking行为对于建立合适的条件和实现成功交配至关重要,因此多配偶行为被认为是罕见的。我们的研究表明,当处子雄性与处子雌性接触时,它们很容易交配,这表明它们有能力在不进行跳跃的情况下交配,而且有可能交配出经过选择的配对。此外,我们还发现,在四小时的时间跨度内,一只雄性个体与至少四只处子雌性个体可以成功交配,而且几乎所有交配都能产生活的后代。我们的研究结果为H. illucens育种项目从大规模选育转向需要控制交配的先进选择性育种设计铺平了道路。与大规模选择相比,这种设计能同时对多个性状进行选择,用于防止近亲繁殖,并能大幅提高选择反应率。
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引用次数: 0
Behavioral Interactions in Two Ant Species in The Southeast United States and Evidence for a Native Supercolony 美国东南部两种蚂蚁的行为相互作用以及本地超级蚁群的证据
Pub Date : 2024-09-10 DOI: 10.1101/2024.09.06.611643
Shreyas Kanwar, Renee Nowicki, Isabella RE Mavourneen, Joshua D Gibson
Ants vary extensively in their colony structure, ranging from occupying single nests to tremendous supercolonies that occupy territories spanning large areas. Fewer than 1% of ants are known to produce supercolonies, yet they are disproportionately overrepresented in highly invasive ants. A broader understanding of supercolonial ants in their native range, therefore, may provide key insights into the factors that allow some ants to become invasive. Here, we show the results of behavioral assays of two native species of ants, Dorymyrmex bureni and D. smithi (Hymenoptera: Formicidae: Dolichoderinae) across geographically separated sites in southeastern Georgia, USA. We show that D. smithi has extremely low incidence of aggression in ants from sites up to 35 km apart, indicating that this may be a supercolonial species. In contrast, we show that D. bureni exhibits high levels of aggression between nest sites. Dorymyrmex smithi is also a temporary social parasite of D. bureni and these two species form mixed nests with no apparent interspecific aggression between workers, but we show that both species interact aggressively in assays within and between sites when the workers are derived from pure species nests. These findings represent an important addition to our knowledge of supercolonial species, and they also lay the groundwork for further studies of the parasitic relationship between these species.
蚂蚁的蚁群结构千差万别,从占据单个蚁巢到占据大片领土的巨大超级蚁群,不一而足。目前已知只有不到 1%的蚂蚁会产生超级蚁群,但它们在高度入侵蚂蚁中的比例却过高。因此,更广泛地了解原生地的超级群体蚂蚁,可能会对某些蚂蚁成为入侵者的因素提供重要的启示。在这里,我们展示了在美国佐治亚州东南部两个地理位置不同的地点对两种本地蚂蚁 Dorymyrmex bureni 和 D. smithi(膜翅目:蚁科:Dolichoderinae)进行行为测定的结果。我们发现,在相距 35 千米的地点,D. smithi 蚂蚁的攻击发生率极低,这表明它可能是一个超级殖民地物种。与此相反,我们发现 D. bureni 在巢穴之间表现出很高的攻击性。Dorymyrmex smithi也是D. bureni的临时社会寄生虫,这两个物种形成混合巢穴,工蚁之间没有明显的种间攻击行为,但我们的研究表明,当工蚁来自纯种巢穴时,这两个物种在巢穴内和巢穴间的试验中都会发生攻击性互动。这些发现是我们对超殖民地物种知识的重要补充,也为进一步研究这些物种之间的寄生关系奠定了基础。
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引用次数: 0
Stopping Speed as State, Not Trait: Exploring Within-Animal Varying Stopping Speeds in a Multi-Session Stop-Signal Task 作为状态而非特征的停止速度:探索多时段停车信号任务中动物内部不同的停车速度
Pub Date : 2024-09-09 DOI: 10.1101/2024.09.05.611370
Jordi ter Horst, Michael X Cohen, Bernhard Englitz
Being able to reactively stop ongoing movements is important for safe navigation through the environment. Reactive stopping is typically studied using the stop-signal task, where participants are occasionally instructed to stop initiated movements. The speed of stopping, also referred to as the stop-signal reaction time (SSRT), is not observable because successful stopping lacks a response, but can be estimated. Researchers most often acquire one session of data per participant to estimate the speed of stopping, but sometimes more sessions of data are acquired to maximize the signal-to-noise ratio, for example when the task is combined with neural recordings such as electrophysiology. However, it is unknown whether the estimated stopping speed is a fixed trait or a state that can vary under identical experimental conditions. In this study, we investigate whether a separately estimated SSRT for each acquired session is statistically meaningful compared to estimating an across-session SSRT, by collecting many sessions in which male rats performed a stop-signal task. Results revealed that within-animal stopping speeds meaningfully changed from session to session and were not following a trend over time (e.g., due to task learning). Single-session SSRT estimates with lower reliabilities were associated with higher go trial response time variabilities, lower skewness levels of the go trial response time distribution, and lower stop accuracies. We also explored which factors explained changing SSRTs, and showed that motivation, shared motor dynamics, and attention could play a role. In conclusion, we encourage researchers to treat SSRTs as state-like variables when collecting multi-session stop-signal task data, as our results have convincingly shown that stopping speeds are far from trait-like under identical experimental conditions. This session-by-session approach will help future research in which neural signatures of reactive stopping need to be extracted in a time-precise manner, because time-locking stop-related neural activity to session-specific SSRTs is expected to capture the signature more precisely as opposed to an across-session SSRT.
能够反应性地停止正在进行的运动对于在环境中安全穿行非常重要。对反应性停止的研究通常采用停止信号任务,即偶尔指示参与者停止已启动的动作。停止的速度也称为停止信号反应时间(SSRT),由于成功停止时没有反应,因此无法观察,但可以估计。研究人员通常会为每位受试者采集一次数据来估算停止速度,但有时也会采集更多的数据来最大限度地提高信噪比,例如当任务与电生理学等神经记录相结合时。然而,在相同的实验条件下,估计的停止速度是一个固定的特征,还是一个可以变化的状态,目前还不得而知。在本研究中,我们通过收集雄性大鼠执行停止信号任务的多个片段,研究了对每个获取片段单独估算的SSRT与估算跨片段SSRT相比是否具有统计学意义。结果表明,动物内部的停止速度在不同阶段会发生有意义的变化,而不是随着时间的推移而变化(例如,由于任务学习)。可靠性较低的单次SSRT估计值与较高的围棋试验反应时间变异性、较低的围棋试验反应时间分布偏度水平和较低的停止准确性有关。我们还探讨了哪些因素可以解释 SSRT 的变化,结果表明,动机、共同运动动力和注意力可能会起到一定的作用。总之,我们鼓励研究人员在收集多时段停止信号任务数据时,将SSRT视为状态变量,因为我们的研究结果令人信服地表明,在相同的实验条件下,停止速度远非特征变量。这种分时段的方法将有助于未来需要以精确的时间方式提取反应性停止神经特征的研究,因为将与停止相关的神经活动与特定时段的 SSRT 进行时间锁定有望比跨时段的 SSRT 更精确地捕捉特征。
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引用次数: 0
Aged mice exhibit faster acquisition of intravenous opioid self-administration with variable effects on intake 老年小鼠静脉注射阿片类药物的自我给药速度更快,但对摄入量的影响各不相同
Pub Date : 2024-09-07 DOI: 10.1101/2024.09.03.611052
Amanda L Sharpe, Laci R Liter, Darius Donohue, Kelsey A Carter, Patricia Vangeneugden, Sofia Weaver, Michael Stout, Michael J Beckstead
Opioid abuse and overdose are major societal issues, and use of opioids among the elderly is increasing at a rapid rate. Despite this increase in opioid use, overdose, and use disorders among the elderly, little is known about abuse potential in a healthy aged population due to technical difficulties with intravenous self-administration in aged rodents. The goal of this study was to address the critical gap in the literature regarding age-dependent differences in opioid (remifentanil and fentanyl) self-administration between old and young mice. Male and female mice were grouped into young (19 weeks) and old (101 weeks) were trained to self-administer intravenous fentanyl or remifentanil in daily sessions. In both old and young mice, acquisition, intake, and cue-responding after forced abstinence were measured for both drugs, and a dose-response curve (remifentanil) and dose-escalation (fentanyl) were conducted. Old mice learned to self-administer both remifentanil and fentanyl faster and more accurately than young mice. While baseline intake was greater in the old compared to young mice self-administering remifentanil, we did not see an increased intake with age at either dose of fentanyl tested. Further, compared to young mice, the old mice showed a greater incubation of responding for cues previously associated with remifentanil after a forced abstinence, but this was not seen for fentanyl. Together these data suggest that an aged population may have an increased drug-abuse vulnerability for opioids compared to young counterparts and underscore the importance of future work on mechanisms responsible for this increased vulnerability.
阿片类药物的滥用和过量是一个重大的社会问题,而老年人使用阿片类药物的人数正在快速增加。尽管老年人使用阿片类药物、用药过量和用药紊乱的情况有所增加,但由于对老年啮齿动物进行静脉自我给药存在技术上的困难,因此人们对健康老年人群滥用阿片类药物的可能性知之甚少。本研究的目的是解决文献中关于老年小鼠和年轻小鼠阿片类药物(瑞芬太尼和芬太尼)自我给药的年龄依赖性差异的重要空白。研究人员将雌雄小鼠分为幼鼠(19周)和老 鼠(101周)两组,每天训练它们自我静脉注射芬太尼或瑞芬太尼。在老龄和幼龄小鼠中,对两种药物的习得、摄入和强迫戒断后的线索反应进行了测量,并绘制了剂量反应曲线(瑞芬太尼)和剂量递增曲线(芬太尼)。老龄小鼠比年轻小鼠更快、更准确地学会了瑞芬太尼和芬太尼的自我给药。虽然与年轻小鼠相比,老年小鼠自我给药瑞芬太尼的基线摄入量更大,但在测试的两种芬太尼剂量下,我们都没有发现摄入量随年龄增长而增加。此外,与年轻小鼠相比,老年小鼠在强迫戒断后对以前与瑞芬太尼相关的线索的反应潜伏期更长,但对芬太尼的反应潜伏期却不长。这些数据共同表明,与年轻小鼠相比,老年群体可能更容易滥用阿片类药物,并强调了今后研究导致这种脆弱性增加的机制的重要性。
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bioRxiv - Animal Behavior and Cognition
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