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Establishing New Isosexual Pairs in Adult Male Guinea Pigs (Cavia porcellus) to Facilitate Social Housing. 在成年雄性几内亚猪(Cavia porcellus)中建立新的异性配对,以促进社会住房。
Pub Date : 2024-03-01 Epub Date: 2024-01-23 DOI: 10.30802/AALAS-JAALAS-23-000086
Jen X Xu, Ashton Coker, Zadie Dulaney, Amelia Furbish, Frank Z Xu, Kristi L Helke, Patrick M Woster, Paul J Nietert, Alicia M Braxton

Guinea pigs (Cavia porcellus) are a commonly used species in biomedical research. As social creatures, compatible guinea pigs should be housed together unless scientific objectives or veterinary care require otherwise. Extensive literature suggests that adult male guinea pigs are highly aggressive in the presence of females, but data are lacking regarding the compatibility of cohoused adult males in the absence of females. Most studies that use adult males do not report housing densities. We used serial wound scoring and observations of behavior to determine whether unfamiliar adult male guinea pigs will develop stable, prosocial isosexual pairs. Wound scoring was performed before and 24 h after pairing. Serial behavioral observations assessed affiliative and agonistic behaviors at 0.5, 2, 24, and 48 h after pairing. Wound scoring and behavioral observations continued weekly for 1 mo and monthly thereafter. Wound scores were significantly higher at 24 h after pairing as compared with baseline and all other time points. Wounding was rare after week 2, indicating reduced aggression. Furthermore, affiliative behaviors significantly increased over time while agonistic behaviors were rare. Together, these data suggest that unfamiliar adult male guinea pigs establish stable prosocial pairs after an acclimation period. As was done in the present study, providing ample space, separate shelters for each animal, and the absence of female guinea pigs will likely facilitate successful pairing. We recommend consideration of a social housing program for adult male guinea pigs to provide companionship and enrich their housing environment.

豚鼠(Cavia porcellus)是生物医学研究中常用的物种。作为社会性动物,除非科研目的或兽医护理另有要求,否则相容的豚鼠应饲养在一起。大量文献表明,成年雄性豚鼠在有雌性豚鼠在场的情况下具有很强的攻击性,但在没有雌性豚鼠在场的情况下,同舍成年雄性豚鼠的相容性却缺乏相关数据。大多数使用成年雄性豚鼠的研究都没有报告饲养密度。我们利用连续的伤口评分和行为观察来确定陌生的成年雄性豚鼠是否会发展出稳定、亲社会的异性配对。在配对前和配对后 24 小时进行伤口评分。在配对后的 0.5、2、24 和 48 小时进行连续行为观察,评估隶属行为和激动行为。伤口评分和行为观察每周进行一次,持续 1 个月,之后每月进行一次。与基线和所有其他时间点相比,配对后 24 小时的伤口评分明显较高。第 2 周后很少出现伤口,表明攻击性降低。此外,随着时间的推移,附属行为明显增加,而攻击行为则很少出现。这些数据表明,陌生的成年雄性豚鼠在经过适应期后会建立稳定的亲社会配对。与本研究一样,为每只豚鼠提供充足的空间、单独的庇护所以及没有雌性豚鼠的情况下,很可能会促进配对的成功。我们建议考虑为成年雄性豚鼠实施社会化饲养计划,为它们提供陪伴,丰富它们的饲养环境。
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引用次数: 0
Effects of Midazolam/Dexmedetomidine with Buprenorphine or Extended-release Buprenorphine Anesthesia in C57BL/6 Mice. 咪达唑仑/右美托咪定与丁丙诺啡或缓释丁丙诺啡麻醉对 C57BL/6 小鼠的影响
Pub Date : 2024-03-01 Epub Date: 2024-02-02 DOI: 10.30802/AALAS-JAALAS-23-000063
Lisa Hagan, Emily M David, Alanna R Horton, James O Marx

The effects of commonly used injectable combinations of anesthetics such as ketamine and xylazine, with or without acepromazine, vary widely across individuals, have a shallow-dose response curve, and do not provide long-term analgesia. These drawbacks indicate the importance of continuing efforts to develop safe and effective injectable anesthetic combinations for mice. In this study, a series of experiments was designed to validate the use of dexmedetomidine and midazolam to provide chemical restraint for nonpainful procedures and the addition of buprenorphine or extended-release buprenorphine to reliably provide a surgical plane of anesthesia in C57BL/6J mice. Loss of consciousness was defined as the loss of the righting reflex (LORR); a surgical plane of anesthesia was defined as the LORR and loss of pedal withdrawal after application of a 300 g noxious stimulus to a hind paw. The combination of intraperitoneal 0.25 mg/kg dexmedetomidine and 6 mg/kg midazolam produced LORR, sufficient for nonpainful or noninvasive procedures, without achieving a surgical plane in 19 of 20 mice tested. With the addition of subcutaneous 0.1 mg/kg buprenorphine or 1 mg/kg buprenorphine-ER, 29 of 30 mice achieved a surgical plane of anesthesia. The safety and efficacy of the regimen was then tested by successfully performing a laparotomy in 6 mice. No deaths occurred in any trial, and, when administered 1 mg/kg atipamezole IP, all mice recovered their righting reflex within 11 min. The anesthetic regimen developed in this study is safe, is reversible, and includes analgesics that previous studies have shown provide analgesia beyond the immediate postsurgical period. Buprenorphine-ER can be safely substituted for buprenorphine for longer-lasting analgesia.

常用的可注射麻醉剂组合(如氯胺酮和异丙嗪,加或不加乙酰丙嗪)在不同个体间的效果差异很大,剂量反应曲线较浅,而且不能提供长期镇痛效果。这些缺点表明,继续努力为小鼠开发安全有效的可注射麻醉组合非常重要。在本研究中,我们设计了一系列实验来验证使用右美托咪定和咪达唑仑为非疼痛性手术提供化学约束,以及添加丁丙诺啡或缓释丁丙诺啡为 C57BL/6J 小鼠提供可靠的手术麻醉平面。意识丧失的定义是右反射丧失;手术麻醉平面的定义是右反射丧失和后爪受到 300 克有害刺激后的蹬地回缩丧失。腹腔注射 0.25 毫克/千克右美托咪定和 6 毫克/千克咪达唑仑可产生 LORR,足以进行无痛或无创手术,但在 20 只小鼠中,有 19 只小鼠在测试中未达到手术平面。在皮下注射 0.1 毫克/千克丁丙诺啡或 1 毫克/千克丁丙诺啡-ER 后,30 只小鼠中有 29 只实现了手术平面麻醉。随后,通过对 6 只小鼠成功实施开腹手术,对该方案的安全性和有效性进行了测试。在所有试验中都没有出现死亡,而且在给小鼠注射 1 毫克/千克阿替帕米唑(IP)后,所有小鼠都在 11 分钟内恢复了右反射。本研究中开发的麻醉方案是安全的、可逆的,并且包含了以往研究表明可在术后立即镇痛的镇痛剂。丁丙诺啡-ER 可以安全地替代丁丙诺啡,以获得更持久的镇痛效果。
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引用次数: 0
Reply to Manuel and Colleagues Letter to the Editor. 回复曼努埃尔和同事致编辑的信。
Pub Date : 2024-03-01 Epub Date: 2024-01-30 DOI: 10.30802/AALAS-JAALAS-23-000121
Michael Eichner, Joanne M Smith
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引用次数: 0
Letter to the Editor Regarding "Assessing Methods for Replacement of Soiled Bedding Sentinels in Cage-level Exhaust IVC Racks" by Eichner and Smith. 致编辑的信,内容涉及 Eichner 和 Smith 撰写的 "评估更换笼级排气式 IVC 架中脏污垫料哨兵的方法"。
Pub Date : 2024-01-30 DOI: 10.30802/AALAS-JAALAS-23-000111
Chris Manuel, Kerith Luchins, Norman C Peterson, Aurore Dodelet-Devillers, Christina Pettan-Brewer, Lise Phaneuf, Joseph P Garner, Megan LaFollette
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引用次数: 0
Reply to Manuel and Colleagues Letter to the Editor. 回复曼努埃尔和同事致编辑的信。
Pub Date : 2024-01-30 DOI: 10.30802/AALAS-JAALAS-23-000121
Michael Eichner, Joanne M Smith
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引用次数: 0
Extended Sanitation Intervals for Cage Components and Automated Watering Valves: Validation and Cost Analysis. 延长笼舍部件和自动浇水阀的卫生间隔:验证和成本分析。
Pub Date : 2024-01-01 Epub Date: 2023-12-09 DOI: 10.30802/AALAS-JAALAS-23-000084
Bryanna Meredith, Bridget M Clancy, Allison Ostdiek, George P Langan, Kerith R Luchins

Although the Guide suggests changing rodent cage components every 2 wk, it states that "decreased sanitation frequency may be justified if the microenvironment in the cages, under the condition of use ..., is not compromised." The purpose of this study was to evaluate extended sanitation intervals of cage components (automated watering valve, wire bar lid, and filter top) of mouse individually ventilated caging (IVCs) at our institution. We hypothesized that there would be no significant difference in relative light units measured by ATP luminometry of these cage components at the control time point of 14 d as compared with each extended time interval: 28, 56, and 84 d. In addition, for automated watering valves, the study was extended to 168 d. We also hypothesized that time-and-motion studies performed by moving to a sanitation interval of 84 d for all components would result in substantial time and cost savings. The components of a total of 24 cages containing 4 or 5 mice each were swabbed, and an ATP luminometer was used to detect organic matter. We found no significant differences in organic matter load between 14 d and all other time points for all cage components. Our time- and cost-savings analysis found that extending the sanitation interval of cage components from every 2 wk (14 d) to every 3 mo (84 d) for every 10,000 cages would save about 3,000 technician hours annually, for a total annual labor cost savings of about $100,000. This study is the first to validate the extended sanitation interval of automated watering valves and confirms the findings of previous studies that validated the extended sanitation frequency of wire bar lids and filter tops of rodent IVCs. Overall, extending the sanitation frequency of cage components reduces workload of animal care staff without compromising the cage microenvironment.

尽管《指南》建议每 2 周更换一次啮齿动物笼子部件,但它指出 "如果笼子中的微环境在使用条件下......没有受到破坏,则可以适当降低消毒频率"。本研究的目的是评估本机构对小鼠独立通风饲养笼(IVC)的笼子部件(自动饮水阀、线棒盖和过滤器顶盖)延长消毒间隔的情况。我们假设,在 14 天的对照时间点与 28、56 和 84 天的延长时间间隔相比,用 ATP 发光测定法测量笼子部件的相对光单位没有显著差异。我们对总共 24 个笼子(每个笼子装有 4 或 5 只小鼠)的各部分进行了拭抹,并使用 ATP 发光器检测有机物。我们发现,在 14 天和所有其他时间点之间,所有笼子部件的有机物含量均无明显差异。我们的时间和成本节约分析发现,每 10,000 个笼子的笼子部件的卫生间隔从每 2 周(14 d)延长到每 3 个月(84 d),每年可节省约 3,000 个技术人员工时,每年可节省约 100,000 美元的劳动力成本。这项研究首次验证了延长自动浇水阀的卫生间隔时间,并证实了之前验证延长啮齿动物 IVC 的铁丝网盖和过滤器顶部卫生频率的研究结果。总之,延长笼子部件的消毒频率可以减少动物护理人员的工作量,同时又不会影响笼子的微环境。
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引用次数: 0
Acute Effects of Hypothermia and Inhalant Anesthesia on Ultrasonic Vocalizations and Neuroendocrine Markers in Neonatal Rats. 低温和吸入麻醉对新生大鼠超声发声和神经内分泌标志物的急性影响。
Pub Date : 2024-01-01 Epub Date: 2023-12-01 DOI: 10.30802/AALAS-JAALAS-23-000008
Katherine A Lamont, Marcella H Boynton, Debra L Hickman, Craig A Fletcher, Morika D Williams

Neonatal rodents undergo anesthesia for numerous procedures and for euthanasia by anesthetic overdose. However, data regarding whether neonatal anesthesia is humane are limited. Hypothermia (cryoanesthesia) is the most commonly used anesthetic protocol for neonatal rats 10 d of age or younger. However, hypothermia has recently been restricted in several countries due to perceived painful effects, including pain on rewarming. Minimizing the potential pain and distress of neonates in research is imperative, although very challenging. Traditional validated and nonvalidated behavioral and physiologic outcome measures used for adult rats undergoing anesthesia are unsuitable for evaluating neonates. Therefore, we investigated the effects of several anesthetic methods on neonatal rats by using the innovative objective approaches of noninvasive ultrasonic vocalizations and more invasive neuroendocrine responses (i. e., serum corticosterone, norepinephrine, glucose). Our results show that hypothermia leads to heightened acute distress in neonatal rats as indicated by prolonged recovery times, increased duration of vocalizations, and elevated corticosterone levels, as compared with neonates undergoing inhalational anesthesia. We demonstrate that inhalational anesthesia is preferable to cryoanesthesia for neonatal rats, and researchers using hypothermia anesthesia should consider using inhalational anesthesia as an alternative method.

新生啮齿动物在许多过程中接受麻醉,并因麻醉过量而安乐死。然而,关于新生儿麻醉是否人道的数据有限。低温(低温麻醉)是10天大的新生大鼠最常用的麻醉方案。然而,最近在一些国家,由于感觉到疼痛的影响,包括重新升温时的疼痛,降低体温已经受到限制。在研究中尽量减少新生儿的潜在疼痛和困扰是必要的,尽管这非常具有挑战性。用于麻醉成年大鼠的传统的经过验证的和未经验证的行为和生理结果测量不适合评估新生儿。因此,我们研究了几种麻醉方法对新生大鼠的影响,采用创新的客观方法,即无创超声发声和更有创的神经内分泌反应(即血清皮质酮、去甲肾上腺素、葡萄糖)。我们的研究结果表明,与吸入麻醉的新生儿相比,低温导致新生大鼠急性窘迫加重,表现为恢复时间延长,发声持续时间增加,皮质酮水平升高。我们证明吸入麻醉比低温麻醉对新生大鼠更可取,使用低温麻醉的研究人员应考虑使用吸入麻醉作为替代方法。
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引用次数: 0
Evaluation of Potential Low-stress Handling Methods in Crl:CDSD Rats (Rattus norvegicus). 评估对 Crl:CDSD 大鼠(Rattus norvegicus)的潜在低压力处理方法。
Pub Date : 2024-01-01 Epub Date: 2023-12-14 DOI: 10.30802/AALAS-JAALAS-23-000009
Jennifer Kylie, Dale M Cooper, Jenna K Kurpinski, Forrest T Chase, Michael D Muzyka, Tyler C Plachta

Low-stress handling methods have been studied in detail in mice, but relatively little research exists concerning preferred handling methods in rats. Most recommendations for low-stress handling of rats have been extrapolated from the mouse literature, despite known differences in handler interaction between the 2 species. The goal of the current study was to evaluate common methods of handling in rats, including application of recognized, low-stress handling methods from other species to rats, in order to determine relative stress levels associated with the handling methods. Seventy male and 70 female, 8-wk-old, Crl:CDSD rats, were housed either individually or in pairs, and were handled weekly or daily using one of the following methods: encircling of the torso (standard thoracic hold), handled using a tunnel, handled using a protective bite glove, handled using a soft paper towel, or tickled prior to being handled by the torso ( n = 10 per sex per treatment group). Body weight and clinical observations were scored at each handling session, abbreviated functional observation batteries were performed every other week, and an interaction test and hematology were conducted prior to study and on the day of study termination. Rats that were socially housed and handled weekly using the standard thoracic hold showed the least evidence of stress, while those that were singly housed and handled weekly using a protective bite glove or tunnel showed the highest level of stress. These effects were predominantly seen in males. This study suggests that standard low-stress handling methods used for other species may not be optimal for rats, and that additional research is needed to identify alternative methods to the standard thoracic hold that would further reduce stress during handling in rats.

对小鼠低应激处理方法进行了详细研究,但有关大鼠首选处理方法的研究相对较少。对大鼠进行低应激处理的大多数建议都是从小鼠文献中推断出来的,尽管已知这两个物种之间在处理者互动方面存在差异。本研究的目的是评估处理大鼠的常用方法,包括将其他物种公认的低应激处理方法应用于大鼠,以确定与处理方法相关的相对应激水平。70只8周大的雄性Crl:CDSD大鼠和70只雌性Crl:CDSD大鼠被单独或成对饲养,每周或每天使用以下方法之一进行处理:环绕躯干(标准胸腔固定)、使用隧道处理、使用保护性咬手套处理、使用软纸巾处理或在处理躯干前搔痒(每个处理组每种性别10只)。每次处理时都对体重和临床观察进行评分,每隔一周进行一次简短的功能观察,并在研究前和研究终止当天进行交互作用测试和血液学检查。每周使用标准胸腔固定法进行社会化饲养和处理的大鼠表现出的应激程度最低,而每周使用保护性咬手套或隧道进行单独饲养和处理的大鼠表现出的应激程度最高。这些影响主要出现在雄性身上。这项研究表明,用于其他物种的标准低应激处理方法可能不是处理大鼠的最佳方法,需要进行更多的研究来确定标准胸腔固定法的替代方法,以进一步减少处理大鼠过程中的应激。
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引用次数: 0
Effects of Refined Handling on Reproductive Indices of BALB/cJ and CD-1 IGS Mice. 精细处理对 BALB/cJ 和 CD-1 IGS 小鼠生殖指数的影响
Pub Date : 2024-01-01 Epub Date: 2023-12-28 DOI: 10.30802/AALAS-JAALAS-23-000028
Margaret A Hull, Elizabeth A Nunamaker, Penny S Reynolds

Current mouse handling methods during cage change procedures can cause stress and potentially compromise animal welfare. Our previous study of breeding C57BL/6J mice found modest increases in pup production and a significant reduction in preweaning litter losses when mice were handled using a tunnel as compared with a tail-lift with padded forceps. The current study evaluated how these 2 handling methods affected reproduction by 2 additional mouse strains, BALB/cJ (a low- to intermediate-fecundity strain) and CD-1 IGS (a high-fecundity stock). We predicted that refined handling would have minimal effects on the high-fecundity line with a satisfactory production rate and greater effects on the low-fecundity line. Handling method (tunnel compared with tail-lift) was randomly assigned to monogamous breeding pairs of mice. Reproductive metrics (litter size at birth and weaning, numbers of litters, litter attrition, between-litter intervals, pup wean- ing weight, and sex ratio) were prospectively monitored for 80 BALB/cJ and 77 CD-1 pairs that were bred continuously for 6 mo. Both strains of mice were highly productive, exceeding previously published breeding data. However, neither strain demonstrated operational or statistically significant differences between handling methods for any reproduction metric. As we detected no negative effects in these 2 strains and the benefits are clear in other strains, refined handling should be considered for all breeding mice.

目前在换笼过程中处理小鼠的方法会造成应激,并可能损害动物福利。我们之前对繁殖 C57BL/6J 小鼠的研究发现,与使用带垫镊子的尾部提升法相比,使用隧道法处理小鼠可适度提高幼鼠产量,并显著减少断奶前的窝产仔损失。目前的研究评估了这两种处理方法对另外两个小鼠品系--BALB/cJ(中低繁殖力品系)和 CD-1 IGS(高繁殖力品系)繁殖的影响。我们预测,精细处理对繁殖率令人满意的高繁殖力品系影响最小,而对低繁殖力品系影响较大。处理方法(隧道与抬尾)被随机分配给一夫一妻制的繁殖小鼠对。对连续繁殖6个月的80对BALB/cJ和77对CD-1小鼠的繁殖指标(出生和断奶时的胎仔大小、胎仔数、胎仔损耗、胎仔间隔、幼仔断奶体重和性别比)进行了前瞻性监测。两个品系的小鼠都具有很高的繁殖能力,超过了之前公布的繁殖数据。然而,这两个品系在任何繁殖指标上的处理方法都没有表现出操作上或统计学上的显著差异。由于我们在这两个品系中没有检测到负面影响,而在其他品系中也有明显的益处,因此应考虑对所有繁殖小鼠进行精细化处理。
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引用次数: 0
Pharmacokinetic Profiles of a New Extended-release Buprenorphine Formulation in Cynomolgus Macaques (Macaca fascicularis). 一种新型丁丙诺啡缓释制剂在猕猴体内的药代动力学特征。
Pub Date : 2024-01-01 Epub Date: 2024-01-02 DOI: 10.30802/AALAS-JAALAS-23-000037
Dania Del I Castillo-Pratts, Clint Rosenfeld, Stephen Kirschner, Elizabeth Nunamaker, David Reim, Cassondra Bauer

The primary objective of this study was to evaluate the pharmacokinetic profile of a new extended-release formulation of buprenorphine (BupBaseER) at a dose that would produce pain management of the desired duration. A secondary objective was to compare the incidence of injection site reactions between the original extended-release formulation (BupHClER) and BupBaseER, which uses a different proprietary polymer-based vehicle than does the BupHClER formulation. Eighteen cynomolgus macaques (M. fascicularis) were divided into 2 groups. Each macaque in the first group (n = 6) received a single subcutaneous injection of 0.06 mg/kg BupBaseER (10 mg/mL) followed at least 2 wk later by a single subcutaneous injection of 0.12 mg/kg. Animals in group 2 (n = 12) received 2 injections of each of 3 compounds-the original polymer matrix vehicle used in BupHClER, the modified polymer matrix vehicle used in BupBaseER, and 0.9% saline-in designated areas of the dorsoscapular region. The 0.06- and 0.12-mg/kg doses both maintained therapeutic levels that were 3 times higher than the hypothesized analgesic threshold of 0.1 ng/mL. These doses maintained therapeutic level for approximately 44 and 103 h, respectively. Based on these data, buprenorphine concentration likely remains well above the therapeutic threshold beyond the 120 h span of this study. During the 30 d after administration, one macaque had a mild skin reaction to BupHClER. None of the animals in either group had skin reactions to BupBaseER at either dosage. These findings support the use of BupBaseER to provide pain management, promote animal welfare, decrease animal stress, and simplify the postoperative management of NHP in research and zoological settings.

本研究的主要目的是评估丁丙诺啡新型缓释制剂(BupBaseER)的药动学特征,其剂量应能在预期时间内达到止痛效果。次要目的是比较原始缓释制剂(BupHClER)和 BupBaseER 的注射部位反应发生率,BupBaseER 使用的专有聚合物载体与 BupHClER 制剂不同。18 只猕猴(M. fascicularis)被分为两组。第一组每只猕猴(n = 6)皮下注射一次 0.06 mg/kg BupBaseER(10 mg/mL),至少 2 周后再皮下注射一次 0.12 mg/kg。第 2 组动物(n = 12)在背胛区的指定区域接受了 3 种化合物(BupHClER 中使用的原始聚合物基质载体、BupBaseER 中使用的改良聚合物基质载体和 0.9% 生理盐水)各 2 次注射。0.06毫克/千克和0.12毫克/千克剂量维持的治疗水平均比假设的镇痛阈值0.1纳克/毫升高3倍。这些剂量的治疗水平分别维持了约 44 小时和 103 小时。根据这些数据,丁丙诺啡的浓度很可能在本研究的 120 小时跨度之后仍远高于治疗阈值。在给药后的 30 天内,一只猕猴对 BupHClER 产生了轻微的皮肤反应。两组动物均未对任何剂量的 BupBaseER 产生皮肤反应。这些研究结果支持在研究和动物园环境中使用 BupBaseER 来控制疼痛、促进动物福利、减少动物压力并简化对 NHP 的术后管理。
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引用次数: 0
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Journal of the American Association for Laboratory Animal Science : JAALAS
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