Prior to use in patients in the clinical setting, the safety, mechanism of action, and efficacy of new treatments must be established. This often requires testing new treatments in animals. Public attitudes toward animal research have been investigated, but less is known about the attitudes of physicians. To begin to address this, we examined attitudes of medical students regarding animal research, and whether these attitudes were rigidly held. We surveyed US-based student members of the American Academy of Neurology (AAN). Students were questioned regarding agreement or disagreement with a set of 14 positively- or negatively-biased statements regarding animal research. To determine if these attitudes were rigidly held, students viewed an educational video regarding animals used in research and repeated the survey immediately after the video. One hundred sixty-eight students completed the initial survey. A group attitude score was calculated based on agreement with 14 statements. Males and those with previous research experience had a significantly more positive attitude toward animal research, but other variables had no effect. After viewing the video, 108 students repeated the survey. The overall attitude of respondents changed to be significantly more positive toward animal research. Of the 14 statements, attitudes toward 7 individual statements became significantly more positive after viewing the video. To our knowledge, this is the first study to examine attitudes toward animal research among medical students. Overall, the group's attitude toward animal research was more positive than negative. However, these negative attitudes do not appear to be rigidly held. These findings should be considered in the future of medical education curriculum development.

Introduced over 20 y ago, IACUCs undertaking postapproval monitoring (PAM) of animal research procedures as a means to ensure researcher compliance is now widely used as an oversight tool in laboratory animal research. Through a literature review evaluating the history of PAM in the United States, discussions of controversy surrounding PAM activities, and reflections on how PAM activities are described within the IACUC community, we present an up-to-date and comprehensive classification system for PAM program methodologies that could serve to standardize how such activities are characterized in IACUC policies, communicated to research staff, used in training programs, implemented for the desired impact by individuals involved in animal research oversight, and referenced by regulatory agencies.

People experience cognitive dissonance when they entertain 2 conflicting ideas at the same time. Cognitive dissonance may cause a negative emotional state, which can lead to engagement of compensation mechanisms to resolve the conflict. Here we describe a survey that explores cognitive dissonance in laboratory animal veterinarians and veterinary technicians and various ways in which veterinary staff manage dissonance associated with research animal use. Respondents—164 veterinarians and 145 veterinary technicians—were asked to rate their opinions of various statements on a sliding scale of 'strongly disagree' to 'strongly agree' or 'never' to 'always.' Statements assessed negative emotions (discomfort, powerlessness, frustration) and compensation mechanisms (devaluing, emotional distancing, shifting responsibility) as bases for inferring effects on welfare states of animals. Responses were evaluated overall and were compared according to level of training (veterinarian compared with veterinary technician), years of work experience (0 to 5, 6 to 10, greater than 10), and species tended (large, mixed, small species). Respondents strongly agreed that animal wellbeing and animal use in research were important. Respondents reported feelings of discomfort, powerlessness, and frustration associated with work. In addition, respondents reported feeling empowered to initiate changes affecting animal welfare. The most frequent compensation mechanism noted was shifting responsibility onto the IACUC and institutional rules. Devaluing the animals was another reported compensation mechanism. Responses to emotional distancing statements were divided. Survey responses supported the existence of cognitive dissonance associated with laboratory animal medicine. Potential negative and positive effects on animal welfare are discussed.

Working with research animals exposes employees to emotionally demanding work and moral stressors. The emotional impact of animal research is similar to that of working with human patients, and is similarly associated with burnout (BNO) or compassion fatigue (CF), which can lead to psychosomatic symptoms, pervasive states of stress, workplace conflict, and at its most extreme, suicidal ideation. One remedy for such feelings is increasing the satisfaction one feels from performing one's job well, known as compassion satisfaction (Csat). To address these occupational health concerns in an academic research setting, the Ohio State University's Lab Animal Resources (ULAR) study team reviewed existing preventative programing both internal and external to the university. Subsequently, a survey was distributed to all staff members to assess the following factors: employee awareness of free resources already available to them, association between staff demographics and the experience of BNO and/or CF, and the employee's own mitigation recommendations. Respondents were mostly female, in 20 to 49 age range, with 0 to 4 y in the field. Of those responding, 81.6% specified that they had experienced BNO and CF alone, together, or in combination with CSat. Factors statistically associated (P < 0.05) with BNO and CF were age, number of years in the field, and number of animals euthanized per year. A relative risk analysis was also used to identify protective factors. Only the age of respondents appeared to be a protective factor— the 50+ age group had 88.57% (RR = 0.1143) reduction in risk for experiencing BNO and/or CF. Participant suggestions indicated that employees would like improvements to the work environment, more novel work experiences, and more positive feedback from department leadership. The social ecological model, a public health model for program interventions, was used as a framework for the development of recommendations to mitigate BNO and CF while increasing CSat. The recommendations were customized for ULAR employees based on the survey findings.

Despite the increasing popularity of zebrafish (Danio rerio) as an animal model, the environmental enrichment preferences of this species have been largely unexplored. We sought to determine the preferences of mature female zebrafish that were singly housed with or without access to one of 10 inanimate forms of enrichment. As a marker of preference, in-tank fish location was observed by video recording. All subjects showed a preference for the front of the tank when caretakers entered the room, demonstrating an effect of human presence on tank location. Among the 10 enrichment items tested, subjects showed the strongest preference for mirrored paper on the side of the tank when compared with the barren half of the tank. Fish also were observed interacting with PVC pipe, marbles, and tulle. Given the preference for enrichment imitating social interaction, we conducted a second study to assess the value of visual exposure of conspecifics in adjacent tanks. The experimental zebrafish were then provided one of 3 conditions—a singly housed neighbor fish, group-housed neighbor fish, or no neighbor fish. All zebrafish housed next to neighboring fish showed a preference to be on the side of the tank nearer to the other fish. Overall, our data indicate that singly housed zebrafish prefer enrichment items that resemble or promote social behaviors. Therefore items such as mirrored paper or housing next to conspecifics should be strongly considered as enrichment strategies for singly housed zebrafish.

Reliable detection of unwanted microbial agents is essential for meaningful health monitoring in laboratory animal facilities. Most rodents at our institution are housed in IVC rack systems to minimize aerogenic transmission of infectious agents between cages. The most commonly used rodent health monitoring systems expose live sentinel rodents to soiled bedding collected from other rodent cages on IVC racks and subsequently test these soiled-bedding sentinels for evidence of infection with excluded agents. However, infectious agents might go undetected when using this health surveillance method, due to inefficient organism shedding or transmission failure. In 2016, our institution switched the health monitoring methodology for the majority of our SPF rodent colonies to real-time PCR testing of environmental samples collected from the exhaust plenums of IVC racks. Here we describe our rationale for this conversion, describe some interesting health monitoring cases that arose soon after the conversion, and discuss a potential problem with the conversion—residual nucleic acids. We compared cost and implementation effort associated with 2 sampling methods, sticky swabs and in-line collection media. We also compared the ability of these 2 sampling methods to detect 2 prevalent microbes in our facilities, Helicobacter and murine norovirus. Our institution-wide switch to health monitoring by real-time PCR assay of exhaust air dust samples thus far has provided a sensitive, simple, and reliable approach for maintenance of SPF conditions in laboratory rodents and has dramatically reduced the use of live sentinel animals.

Providing postoperative analgesia to rats by oral administration, compared with injections, reduces stress from frequent handling and is technically easier for investigators. The purpose of this study was to investigate whether bacon-flavored tablets containing gabapentin, carprofen or a combination of both drugs effectively attenuates postoperative mechanical and thermal hypersensitivity in a rat model of incisional pain. Forty-eight Sprague–Dawley rats were randomly assigned to 1 of 5 treatment groups: placebo tablet; a single, subcutaneous injection of buprenorphine sustained release at 1.2 mg/kg; gabapentin 90 mg/tablet; carprofen 5 mg/tablet; gabapentin 90 mg and carprofen 5 mg/tablet (gabapentin/carprofen). Tablets were given to rats on days -3, -2, -1, 0 (surgery), 1, and 2. Rats were anesthetized using isoflurane. A 1 cm skin incision was made aseptically on the plantar surface of the left hindpaw and closed by using suture. Mechanical (von Frey monofilament) and thermal (Hargreaves method) hypersensitivity were tested daily, and analyzed on days -1, 1, 2, and 3. The amount of tablet consumed was recorded daily; postoperatively rats consumed 101 to 133 mg/kg of gabapentin, 5.5 to 5.8 mg/kg of carprofen, and 86-137/1.9-3 mg/kg of gabapentin/carprofen, respectively. Both the gabapentin and carprofen groups displayed attenuated mechanical hypersensitivity on all 3 postsurgical days and decreased thermal hypersensitivity on Day 3. The gabapentin/ carprofen group showed attenuated mechanical hypersensitivity on Day 2 and 3, but no significant reduction of thermal hypersensitivity. These data suggest that both gabapentin and carprofen, given orally by flavored tablet, effectively attenuate postoperative mechanical hypersensitivity for 3 d after surgery in a rat model of incisional pain.

Alfaxalone is an injectable anesthetic agent that is used in veterinary medicine for general anesthesia. We evaluated the safety and efficacy of alfaxalone delivered through continuous rate infusion by comparing ketamine–xylazine–alfaxalone (KXA) anesthesia with ketamine–xylazine (KX) anesthesia in Sprague–Dawley rats. Anesthesia was induced in male and female rats by using subcutaneous KX. After induction, rats in the KXA group received alfaxalone (10 mg/kg/h IV) for 35 min, whereas rats in the KX group did not receive alfaxalone. At the end of the trial, alfaxalone was discontinued, and xylazine was reversed in all rats by using atipamezole. Throughout anesthesia, we assessed forepaw withdrawal reflex (FPWR), hindpaw withdrawal reflex (HPWR), response to surgical stimulation, heart rate, respiratory rate, SpO₂, body temperature, and time to standing. KXA produced a reliable surgical plane of anesthesia, as evidenced by the loss of both FPWR and HPWR and lack of response to surgical stimulation in all 16 rats, whereas only 6 of the 16 rats in the KX group lost HPWR. No rat in the KXA group regained a paw withdrawal reflex during alfaxalone administration, whereas 3 of the 12 rats (25%) in the KX group that reached a surgical plane of anesthesia exited that plane within the 35-min timeframe. Neither heart rate, respiratory rate, SpO₂, body temperature, nor time to standing differed between KXA and KX groups; and there were no sex-associated differences in anesthesia response. These results indicate that alfaxalone (10 mg/kg/h IV) delivered through continuous rate infusion, in combination with ketamine and xylazine, provides a safe, prolonged, and reliable surgical plane of anesthesia in rats.

New Zealand white rabbits (Oryctolagus cuniculus) are an established in vivo model for the study of structural and functional consequences of vocal-fold vibration. Research design requires invasive laryngotracheal procedures, and the presence of laryngospasms or pain responses (or both) hinder phonation-related data collection. Published anesthesia regimens report respiratory depression and muscle tone changes and have been unsuccessful in mitigating autonomic laryngeal responses in our protocol. Infusion of ketamine hydrochloride and dexmedetomidine hydrochloride in pediatric medicine provides effective analgesia and sedation for laryngotracheal procedures including intubation and bronchoscopy; however, data evaluating the use of ketamine–dexmedetomidine infusion in rabbits are unavailable. This study reports a new infusion regimen, which was used in 58 male New Zealand white rabbits that underwent a nonsurvival laryngotracheal procedure to induce phonotraumatic vocal-fold injury. Animals were sedated by using ketamine hydrochloride (20 mg/kg IM) and dexmedetomidine (0.125 mg/kg IM). Maintenance anesthesia was provided by using continuous rate intravenous infusion of ketamine hydrochloride (343 μg/kg/min) and dexmedetomidine (1.60 μg/kg/min). A stable plane of anesthesia with no autonomic laryngeal response (laryngospasm) was achieved in 32 of the 58 rabbits (55%). Laryngospasms occurred in 25 of 58 animals (43%) and were controlled in 20 cases (80%) by providing 0.33 mL 2% topical lidocaine, incremental increase in infusion rate, or both. Continuous rate infusion of ketamine hydrochloride–dexmedetomidine with prophylactic topical lidocaine provides a predictable and adjustable surgical plane of anesthesia, with minimal confounding respiratory and autonomic laryngeal responses, during extended-duration laryngotracheal surgery in rabbits. This regimen should be considered as an alternative to injection maintenance for prolonged, invasive procedures.

Effective pain relief in animals relies on the ability to discern pain and assess its severity. However, few objective measures exist to assess the presence and severity of pain in axolotls, and few resources are available regarding drugs and appropriate doses to provide pain relief in this species. This study evaluated behavioral tools for cageside pain assessment and validated a reproducible and reliable quantitative method to evaluate analgesic efficacy in axolotls. Animals were divided into control and treatment groups (n = 6 per group); treatment groups received buprenorphine through injection (50 mg/kg every 24 h for 48 h intracelomically) or butorphanol immersion (0.50 or 0.75 mg/L every 24 h for 48 h). Qualitative behavioral tests, adapted from other amphibian studies, included tapping on the home tank, directing water jets or physically touching specific anatomic points on the animal, and placing a novel object in the home tank. Quantitative methods used to produce noxious stimuli were the acetic acid test and von Frey aesthesiometers. Animals that were treated with analgesics did not demonstrate a significant difference compared with controls during behavioral assessment at 1, 6, 12, 25, 30, and 48 h after analgesia administration. The acetic acid test revealed a reproducible, concentration-dependent pain response. However, a significant difference in the AAT response was not observed between control and treated groups with the tested analgesics and doses.

Studies of visual responses in isoflurane-anesthetized mice often use the sedative chlorprothixene to decrease the amount of isoflurane used because excessive isoflurane could adversely affect light-evoked responses. However, data are not available to justify the use of this nonpharmaceutical-grade chemical. The current study tested whether pharmaceutical-grade sedatives would be appropriate alternatives for imaging pupillary light reflexes. Male 15-wk-old mice were injected intraperitoneally with 1 mg/kg chlorprothixene, 5 mg/kg acepromazine, 10 mg/kg chlorpromazine, or saline. After anesthetic induction, anesthesia maintenance used 0.5% and 1% isoflurane for sedative- and saline-injected mice, respectively. A photostimulus (16.0 log photons cm^–2 s^–1; 470 nm) was presented to the right eye for 20 min, during which the left eye was imaged for consensual pupillary constriction and involuntary pupil drift. Time to immobilization, loss of righting reflex, physiologic parameters, gain of righting reflex, and degree of recovery were assessed also. The sedative groups were statistically indistinguishable for all measures. By contrast, pupillary drift occurred far more often in saline-treated mice than in the sedative groups. Furthermore, saline-treated mice took longer to reach maximal pupil constriction than all sedative groups and had lower heart rates compared with chlorpromazine- and chlorprothixene-sedated mice. Full recovery (as defined by purposeful movement, response to tactile stimuli, and full alertness) was not regularly achieved in any sedative group. In conclusion, at the doses tested, acepromazine and chlorpromazine are suitable pharmaceutical-grade alternatives to chlorprothixene for pupil imaging and conceivably other in vivo photoresponse measurements; however, given the lack of full recovery, lower dosages should be investigated further for use in survival procedures.

Objectively recognizing postoperative pain in mice is challenging, making it difficult to determine an appropriate postoperative analgesic regimen. Adult male mice produce ultrasonic vocalizations after exposure to adult female urine (FiUSV). To determine if FiUSV can be used as a indicator of postoperative pain, FiUSV produced by male C57BL/6J mice were assessed for 5 d before and after vasectomy or sham surgery with or without sustained-release buprenorphine. Postoperative pain was assessed by monitoring vocalization using an ultrasonic microphone and by evaluating orbital tightness, posture, and piloerection at postoperative time points. Before vasectomy or sham surgery, 25 of 38 male mice produced FiUSV on 4 of 5 d (143 ± 93 FiUSV). Vasectomized mice without postoperative analgesia produced significantly fewer FiUSV (59 ± 26 FiUSV) compared with baseline (212 ± 102 FiUSV) at 4 h postoperatively, but returned to baseline by 28 h. Vasectomized mice treated with buprenorphine and sham-surgery mice had no change in FiUSV from baseline at any time point after surgery. Activity was decreased compared with baseline in vasectomized mice, regardless of receiving postoperative analgesia or not, but only at the 4-h time point. There were no differences in behavior scores between vasectomized mice and sham-surgery mice at any time point. These results show that FiUSV can be used to detect postoperative pain in male C57BL/6J mice after vasectomy.

Ulcerative dermatitis in laboratory mice remains an ongoing clinical problem and animal welfare issue. Many products have been used to treat dermatitis in mice, with varying success. Recently, the topical administration of healing clays, such as bentonite and green clays, has been explored as a viable, natural treatment. We found high concentrations of arsenic and lead in experimental samples of therapeutic clay. Given the known toxic effects of these environmental heavy metals, we sought to determine whether the topical administration of a clay product containing bioavailable arsenic and lead exerted a biologic effect in mice that potentially could introduce unwanted research variability. Two cohorts of 20 singly housed, shaved, dermatitis free, adult male CD1 mice were dosed daily for 2 wk by topical application of saline or green clay paste. Samples of liver, kidney and whole blood were collected and analyzed for total arsenic and lead concentrations. Hepatic and renal concentrations of arsenic were not different between treated and control mice in either cohort; however, hepatic and renal concentrations of lead were elevated in clay treated mice compared to controls in both cohorts. In addition, in both cohorts, the activity of δ-aminolevulinate acid dehydratase, an enzyme involved with heme biosynthesis and a marker of lead toxicity, did not differ significantly between the clay-treated mice and controls. We have demonstrated that these clay products contain high concentrations of arsenic and lead and that topical application can result in the accumulation of lead in the liver and kidneys; however, these concentrations did not result in measurable biologic effects. These products should be used with caution, especially in studies of lead toxicity, heme biosynthesis, and renal α2 microglobulin function.

Infrared thermometry (IRTM) is a noncontact method to measure temperature. The purpose of this study was to compare rectal temperature and IRTM in healthy anesthetized swine, with the hypothesis that IRTM would be an accurate, noninvasive alternative for rectal temperature measurement. Two groups of female Yorkshire-cross swine (n = 14 and n = 12) were sedated with Tiletamine–zolazepam (0.5 mg/kg) for blood collection during a routine physical examination. While sedated, rectal temperatures were measured using a SureTemp Plus 690 (Welch Allyn) and IRTM measurements were taken using a FLIR E5 thermal imaging camera. The 2 anatomic sites used for thermography measurements were the area surrounding the eye and the neck at the base of the ear. The distance from the imaging camera and the animal during IRTM measurements was 24 to 32 inches, a distance that would allow camera access in a standard swine enclosure. The infrared imaging camera's surface temperature measurement exhibited a proportional bias when compared with the rectal temperature. All rectal temperature measurements were between 98.7 °F to 101.3 °F, with a mean temperature of 100.4 °F. IRTM tended to underestimate rectal temperatures at lower values, and overestimate rectal temperatures at higher values by approximately (+) or (-) 0.8 °F of rectal temperature. Infrared thermometry can provide a quick noninvasive assessment of the body surface temperature, without the need for animal handling or restraint, but should not be considered an accurate replacement for rectal temperature measurement.