Journal of the American Association for Laboratory Animal Science : JAALAS最新文献

Compounded sustained-release buprenorphine (SRB) has historically been used at our institution for postoperative analgesia in African green monkeys (AGMs), but it is not FDA approved and lacks species-specific data. With the recent FDA indexing of pharmaceutical-grade extended-release buprenorphine (EXR; Ethiqa XR; Fidelis), we aimed to compare the pharmacokinetic (PK) profile using serial plasma sampling up to 96 hours and postoperative analgesic efficacy of EXR compared with SRB. A total of 10 AGMs (n = 5 per test article) received 0.2 mg/kg SC of either EXR or SRB to complete the PK study. For the efficacy study, 20 animals (n = 10 per test article) were monitored for 3 days postoperatively after EEG telemetry surgery with femoral artery catheterization for behavioral indicators of pain and adverse effects. Plasma buprenorphine levels were analyzed using liquid chromatography-tandem mass spectrometry. PK study observations included appetite, fecal output, and injection site reactions. Both formulations achieved plasma concentrations above the presumed therapeutic threshold (0.1 ng/mL) for up to 96 hours. SRB produced higher mean plasma levels at early time points (30 minutes, 4 hours), but the overall PK profiles were similar. Injection site reactions were minimal and resolved spontaneously. For the efficacy assessment, clinical observations were evaluated using a postoperative score sheet. No significant differences were observed in postoperative pain scores between groups. Both EXR and SRB at 0.2 mg/kg SC provided sustained therapeutic plasma levels up to 96 hours and were well tolerated in AGMs, with comparable efficacy in postoperative pain control. EXR offers a compliant and effective alternative to compounded SRB for analgesia in AGMs, supporting its use in laboratory settings and regulatory compliance with current guidelines.

Jugular vein (JV) blood sampling is widely employed in pharmacological, toxicological, and pharmacokinetic studies due to its ability to provide large and repeatable blood volumes. However, current approaches are constrained by low convenience, safety concerns, and variable sample quality. Here, we report the development of a new single-operator JV blood sampling technique for conscious rats. By optimizing animal restraint, puncture site localization, and procedural standardization, the method significantly reduced sampling time, puncture attempts, pain-related behaviors, and hemorrhagic injury, while ensuring consistent blood yield. Compared with the conventional approach, it achieved a 100% success rate, halved the average sampling time, and maintained stable serum biochemical, coagulation, and hematologic parameters. The utility of this method was further confirmed in an intraperitoneal glucose tolerance test and a cisplatin-induced acute kidney injury model, where data consistency was preserved. This technique provides a convenient, safe, and reliable alternative for repeated blood collection in conscious rats, ensuring animal welfare and supporting the generation of high-quality data in preclinical research.

Single housing of animals, or social isolation, is a known stressor for many species. Generally, laboratory animals are housed in social groups as a default to support their behavioral welfare. In some research protocols, investigators may request exemptions from social housing policies after surgical procedures due to concerns that cohoused animals may damage implanted devices, remove each other's wound closures, or cause other stress or injury that may interfere with the study. However, the practice of singly housing postoperative animals may result in greater stress for animals and unintended consequences for research being conducted. Therefore, the IACUC or relevant ethical body should judiciously consider any request for single housing and require adequate justification for making this exception. This review discusses the social nature of some common research animals, the research effects of single housing, the regulatory requirements for social housing, and successful cases of socially housing postoperative and/or instrumented animals in the research setting with the goal of promoting social housing of postoperative animals.

Limited information exists regarding propofol's use as a total intravenous anesthesia in cynomolgus monkeys. This study investigated the continuous rate infusion (CRI) of propofol to provide light anesthesia during nociceptive testing. We hypothesized that a CRI of propofol would effectively induce light anesthesia in cynomolgus macaques during repeated weeks of C-fiber nociceptive (heat) stimulation. Four male cynomolgus monkeys were anesthetized with ketamine/dexmedetomidine (4 and 0.02 mg/kg, respectively, IM). Following intravenous catheter placement, atipamezole (0.5 mg/kg SC) was administered to reverse the effect of dexmedetomidine, and a propofol CRI (8-16 mg/kg/h) was initiated. Physiologic parameters, including systolic, diastolic, and mean arterial pressure, heart rate, respiratory rate, peripheral oxygen saturation, and body temperature, were recorded continuously. Animals were maintained with 100% oxygen via a mask and an intravenous electrolyte (Normosol-R; 5-10 mL/kg/h) infusion. Two hours after ketamine/dexmedetomidine administration, propofol doses were incrementally adjusted to elicit withdrawal reflexes using argon laser nociceptive (heat) stimulation (on digital pads of the forearms) with 5- to 15-minute intervals between stimulations. Propofol doses and physiologic parameters were recorded every 15 minutes. Following the baseline testing, the animals underwent a surgical procedure between sessions 1 and 2. Anesthesia and nociceptive stimulation were conducted over 6 nonconsecutive weeks. Test results showed that over the 6-week period the propofol doses remained unchanged, with variations not reaching statistical significance, and the physiologic parameters did not exhibit significant differences. These findings suggest that a propofol CRI of 8 to 16 mg/kg/h effectively provides light anesthesia in cynomolgus macaques during repeated nociceptive (heat) stimulation.

Humans work with animals in many different ways. In some contexts, animals are allowed to 'retire' and be rehomed in sanctuaries or private homes when they are no longer able or needed to work. Similarly, laboratory animals can be rehomed at the end of a study. However, there is relatively little research on stakeholders' perceptions of rehoming. We explored the views of three key groups: the people who adopt these animals, the animal technicians who care for these animals prior to rehoming, and the researchers who are normally responsible for most of the interactions between people and these animals. To do this, we carried out a thematic analysis of semistructured interviews. Our aim was to obtain insights that could inform reflection and guide future research priorities around rehoming programs. Our study demonstrated support for laboratory rat rehoming in all stakeholder groups. Rehomers' and technicians' comments focused chiefly on the potential benefits of rehoming to the animal and benefits to institutional openness. Researchers made similar comments, but these were tempered by concerns around the welfare of the animals after rehoming, the fate of animals that cannot be rehomed, rehomers' health and wellbeing, and the potential risks associated with the transparency of individual's and the institution's use of animals in research. We discuss these themes in the context of the ethics of laboratory animal use, manifesting a culture of care, and challenges around enhancing institutional openness on animal research.

Ethiqa XR is an FDA-indexed, extended-release, lipid-bound buprenorphine formulation providing 72 hours of opioid analgesia with a 90-day postbroach discard date. For small rodent studies, the standard vial frequently provides more drug than can be used within the 90-day labeled discard date, which can limit cost-effectiveness for researchers. This study evaluated whether sterility could be preserved for an additional 90 days beyond the labeled discard date through monthly testing for bacterial and fungal contamination, in addition to the presence of endotoxins. Twice weekly, each vial was wiped with 70% isopropyl alcohol, and a 20-gauge needle was inserted and then withdrawn, with samples removed from the vials at time points up to 180 days. All vials consistently remained free of bacterial, fungal, and endotoxin contamination throughout the study period and were sterile up to the final assessment at 180 days postbroaching. The concentration or efficacy of Ethiqa XR were not evaluated during this study.

Cage changes can be a stressful period in a mouse's life due to the rapid change of environment. It is essential to study the behavioral effects of a cage change on mice, including drinking, eating, aggression, and sleep, as these can affect research variability. This study evaluated the effects of a cage change on behavior and whether transferring nesting material could mitigate the negative effects of a cage change. Using home cage monitoring with computer vision artificial intelligence (AI), 40 C57BL/6 mice were continuously monitored for 2 consecutive cage changes. Mice received either new nesting material (control) or transferred soiled nesting material at cage change. Data were analyzed before and after a cage change and reported for at least 3 days or until baseline behavior resumed. Parameters collected included time spent drinking, eating, sleeping, and aggression. Two hours after a cage change, drinking and eating significantly increased, and sleep significantly decreased compared with pre-cage change values. Long-term effects ranged from decreased sleep in the first 24 hours to decreased eating for 3 days post-cage change. Total distance traveled was increased up to day 4 post-cage change, and rearing time was increased for 3 days after a cage change. All significant behaviors gradually stabilized by day 5. Transfer of old nesting material had no significant impact at any time point. These results show that there are both long-term and short-term effects of a cage change, and nest transfer may not influence these parameters in C57BL/6 mice.

Corynebacterium bovis is an opportunistic bacterium that infects the skin of immunodeficient mice used in biomedical research. C. bovis was first deemed clinically significant in the mid-1990s. To date, only limited data are available on the prevalence of this infection among research institutions in the United States. Here we define prevalence as the proportion of institutions that have C. bovis-infected mice in their care. To determine the national prevalence of C. bovis infections, we performed a survey of animal resource program directors and veterinarians at the NIH top 50 funded academic institutions and all Designated Cancer Centers of the National Cancer Institute. This survey was initially performed in 2015 and then expanded and repeated in 2023. Survey questions assessed institutional C. bovis status (positive, negative, or unsure), surveillance practices, and attempts to establish C. bovis-free colonies through bioexclusion. Responses were obtained from 81 institutions in 2015 and 85 in 2023, achieving 100% participation in both years. Between 2015 and 2023, C. bovis-positive status declined slightly (49% to 45%), negative responses dropped more sharply (38% to 22%), and uncertainty increased (12% to 33%), resulting in an overall shift in response distribution (P = 0.002). Despite the increased uncertainty, 69% (59/85) of all institutions in 2023 performed active surveillance for C. bovis in some form. Similarly, of institutions that self-report as having C. bovis-infected mice, 84.2% (32/38) performed C. bovis surveillance, and 78.9% (30/38) have used bioexclusion techniques. Overall, 71.7% (61/85) of institutions recognize C. bovis as an actionable pathogen. Conversely, between 20% and 28% (17 and 24/85) of institutions in 2023 did not see C. bovis as an actionable pathogen and, if present, chose to tolerate it.

Rodents are highly susceptible to peri-anesthetic hypothermia because of their small body size, large surface area to volume/mass ratio, and anesthetic-induced thermoregulatory depression. Early heat loss during induction is rapid and can be difficult to reverse, emphasizing the need for simple, reliable warming solutions during anesthetic induction. We designed and validated a low-cost, Arduino-controlled heated induction chamber for mice and evaluated its safety and efficacy in preventing early hypothermia. The device uses proportional integral derivative control to regulate a heated chamber floor. Bench testing quantified warm-up time, steady-state stability, and the temperature offset between the embedded thermistor and surface temperature. In a randomized, paired, repeated-measures design, 10 adult C57BL/6 mice underwent 2 experimental conditions, unheated induction compared with heated induction, followed by a standardized 10-minute anesthetic maintenance phase on a prewarmed, heated surgical monitoring platform. Core body temperature was measured with intraperitoneal radio frequency identification transponders, while rectal temperature and physiologic parameters (peripheral oxygen saturation, heart rate, respiratory rate) were recorded during maintenance. Recovery time was measured from isoflurane discontinuation until the first voluntary movement. The heated chamber reached thermal stability within 10 minutes; at steady state, a constant average surface temperature near 37.5 °C was reliably obtained. During induction, unheated controls showed a rapid decline in core temperature, while during the heated-chamber induction, they maintained normothermia. The control group did not regain baseline temperature until several minutes into the maintenance phase and stabilized at values ∼1 °C lower than those of the heated group. Both groups remained physiologically stable during anesthetic maintenance and recovered within comparable times. This cost-effective, Arduino-based chamber prevented early hypothermia without compromising physiologic stability and represents a practical refinement to improve rodent anesthetic procedures, animal welfare, and experimental reproducibility.

Tunnel handling is a widely recommended, less-aversive method for improving laboratory mouse welfare by reducing handling-induced anxiety. While its effects on behavioral tests and physiologic outcomes have been reported, little is known about its impact on stress responses to brief restraint procedures commonly used in daily health checks and experimental work. This study aimed to investigate whether tunnel or tail handling influences the physiologic stress response of mice following a brief scruff restraint. Female BALB/c mice were assigned to one of 4 groups combining 2 handling methods (tail or tunnel) with or without a 10-second scruff restraint. Both single and repeated restraint procedures were evaluated separately. Voluntary interaction with the handling device was used to assess the suitability of the handling method. Plasma corticosterone (pCORT) concentrations were measured 20 minutes after restraint to evaluate the physiologic stress response. Tunnel-handled mice showed longer voluntary interaction times than tail-handled mice, indicating reduced handling aversion. Scruff restraint increased pCORT concentrations in both tail- and tunnel-handled mice. However, the handling method did not significantly affect pCORT concentrations following either single or repeated restraint. These findings suggest that the handling method has minimal impact on physiologic stress following brief restraint, supporting the use of less-aversive handling techniques without concern for confounding stress effects.