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

A critical component of an animal care biosecurity plan includes the sterilization of materials that come into direct contact with the animals. Dry-heat sterilization is gaining popularity in animal research facilities due to lower cost, less space utilization, no water usage, and the ability to sterilize water-sensitive materials. Currently, dry-heat sterilization ovens are validated against Bacillus atropheus spore strips with the assumption that a lack of sporulation is equivalent to successful sterilization. However, no published studies describe sterilization of rodent cages that contain relevant rodent pathogens by using this method. To determine if a dry-heat sterilizer can sterilize rodent cages and bedding against relevant rodent pathogens, we created murine norovirus (MNV)-contaminated cages by using mice with known MNV infection and shedding. The contaminated cages were either sterilized with the dry-heat sterilizer or not sterilized. Naïve, 4-wk-old, CD-1 mice were placed in the dry-heat-sterilized cages, contaminated unsterilized cages, or standard autoclaved cages for 2 wk. The mice were subsequently placed into clean, autoclaved cages for the remainder of the study. Fresh fecal pellets were collected at weeks 0, 12, and 16 and submitted for MNV PCR. Whole blood was collected for MNV serology at weeks 0, 8, 12, and 16. At week 16, all mice that had been in the unsterilized contaminated cages were positive for MNV by both fecal PCR and serology, whereas the mice in the dry-heat-sterilized and autoclaved cages were negative for MNV by both methods at all time points. Our study supports the use of dry heat sterilization as a viable sterilization method for rodent cages and bedding.

Naked mole rats (Heterocephalus glaber) are a unique rodent species originating in Africa and are increasingly being used in research. Their needs and characteristics differ from those of other rodents used in research. Unique housing systems are necessary to address the special macro- and microenvironmental requirements of NMRs. Naked mole rats are one of the 2 known eusocial mammalian species, are extremely long-living, are active burrowers, and are accustomed to a subterranean environment. Unlike typical rats and mice, naked mole rats need specific, unique housing systems that mimic their natural subterranean environment to support health and longevity. Here we provide an overview of naked mole rats and a housing method that can be used in research settings.

Rabbits are a common companion animal and research subject and frequently require sedation to facilitate procedures. The objective of this study was to compare the effects of intramuscular butorphanol and midazolam combined with either alfaxalone or ketamine in rabbits. In a complete crossover study, healthy New Zealand white rabbits (n = 9; age, 6 mo) randomly received midazolam (1 mg/kg IM) and butorphanol (1 mg/kg IM) combined with either alfaxalone (2 mg/kg IM; ABM) or ketamine (5 mg/kg IM; KBM). Time to first effects, recumbency, and standing (recovery) were recorded. Every 5 min during recumbency, an investigator who was blind to treatment group collected serial physiologic parameters and sedation scores. At 5 min after rabbits became recumbent, manipulations were performed to mimic 2-view radiography and a cephalic intravenous catheter was placed. At 30 min after drug injection, flumazenil (0.05 mg/kg IM) was administered for reversal. Food consumption and fecal output were measured for 3 d after each study day. Time to standing and duration of recumbency differed significantly between groups. The median (range) of the total sedation score for ABM was 10 (8 to 10) and for KBM was 10 (6 to 10). Sham radiographs were successful in all rabbits in both groups. Physiologic parameters were not significantly different between groups over time. At 24 h after drug treatment, KBM-treated rabbits showed reduced food intake and both groups showed reduced fecal output. Total sedation scores decreased significantly over time in KBM rabbits ( P < 0.001) but not in ABM rabbits (P = 1). The duration of recumbency was significantly longer in ABM rabbits than in KBM rabbits. Both protocols produced sufficient sedation for radiograph acquisition without clinically significant adverse effects.

Noninvasive blood pressure measurement devices have gained popularity in recent years as an alternative to radiotelemetry and other invasive blood pressure measurement techniques. While many factors must be considered when choosing a measurement method, specific variables should be evaluated when using a tail-cuff blood pressure technique. Rodents have complex and dynamic thermal biology processes that involve fluctuating vasomotor tone of the tail. This and other factors that affect vascular tone, such as the autonomic response to stress, significantly affect peripheral blood flow. Awareness and consideration of thermoregulatory states and vasomotor tone can increase success and decrease variability when measuring blood pressure measurements using a tail-cuff measurement technique.

Buprenorphine is perhaps the most prescribed analgesic for management of postoperative pain in mice. Although various buprenorphine formulations are effective in commonly used immunocompetent mouse strains, a knowledge gap exists regarding its efficacy in immunodeficient mice. Here we used a plantar incision to evaluate the efficacy of 3 buprenorphine formulations for attenuating postoperative mechanical and thermal hypersensitivity in the immunodeficient NSG mouse strain. We also characterized the pharmacokinetics of these formulations over a 72-h period. We hypothesized that all 3 buprenorphine formulations evaluated-the standard preparation and 2 extended-release products (Bup-HCl, Bup-ER, and Bup-XR, respectively)-would attenuate postoperative mechanical and thermal hypersensitivity resulting from a plantar incision in NSG mice. Male and female NSG mice (n = 48) were allocated to 4 treatment groups: saline (0.9% NaCl, 5 mL/kg SC once); Bup-HCl (0.1 mg/kg SC, BID for 2 d); Bup-ER (1.0 mg/kg SC once); and Bup-XR (3.25 mg/kg SC once). Mechani- cal and thermal hypersensitivity assessments were conducted 24 h before surgery and at 4, 8, 24, 48, and 72 h afterward. All groups of mice showed mechanical and thermal hypersensitivity within the first 24 h after surgery. Behavioral pain indicators (guarding, toe-touching [intermittent partial weight bearing], licking the incision, vocalizations) were observed in some mice from each group at every postoperative time point. Plasma buprenorphine was measured in a separate group of mice and concentrations surpassed the suggested therapeutic level (1.0 ng/mL) for less than 4 h for Bup-HCl, for at least 24 h for Bup-ER, and for 72 h for Bup-XR. Our results indicate that at the dosages studied, these buprenorphine formulations do not adequately attenuate postoperative mechanical and thermal hypersensitivity in the plantar incisional model in NSG mice. These findings support the need for strain-specific analgesic protocols for mice used in research.

Buprenorphine is commonly used to control postoperative pain in rodents. Short-acting formulations of buprenorphine (bup-HCl) require frequent handling and restraint of animals for appropriate dosing, which can be stressful and confound research outcomes. Ethiqa XR (bup-ER) is an FDA-indexed extended-release buprenorphine formulation that is an alternative to bup-HCl in mice and rats. In the current study, we first evaluated the pharmacokinetics of bup-ER in male C57BL/6J mice by sampling blood at 10 time points, ranging from 30 min to 72 h after administration (n = 3 mice per time point). Average plasma concentrations fell below therapeutic levels at 48 h after administration. We also evaluated the safety of bup-ER when administered prior to surgery in combination with common anesthetics and the efficacy of bup-ER in mouse laparotomy. Anesthetic safety was studied by measuring respiratory rate, rectal temperature, and recovery time in groups of mice (n = 8) given bup-HCl, bup-ER, or saline in combination with isoflurane or ketamine-xylazine anesthesia. No differences were seen between analgesic treatment groups with either of the general anesthetics. To evaluate efficacy, mice (n = 10) were randomly allocated to receive either bup-ER (3.25 mg/kg) once presurgically, bup-HCl (0.1 mg/kg) presurgically and then every 8 h, or saline once before surgery. Mice underwent a sham laparotomy and were assessed for pain based on changes in weight, cageside ethogram, nesting consolidation test, rearing frequency, and nociception to von Frey testing at 6, 12, 24, 48, and 72 h after surgery. Cageside ethogram, rearing frequency, and von Frey testing showed significant differences between bup-ER-treated mice and saline controls in the early postoperative period. No significant effects between treatment groups were seen in daily weights or nesting consolidation scores. This study demonstrates that bup-ER can be safely administered before surgery and provides analgesia for up to 48 h after administration based on pharmacokinetic and behavioral data.