In response to pain, mice may vocalize at frequencies above the range of human hearing (greater than 20 kHz). To determine whether an ultrasonic recording system is a reliable tool for assessing acute pain, we measured audible and ultrasonic vocalization in mice subjected to either
nonpainful or potentially painful procedures performed routinely in animal facilities. Data were collected from 109 weanling mice (Mus musculus; B6, 129S6-Stab 5b) scheduled for 2 potentially painful procedures: DNA testing by tail snip and identification by ear notching. The mice each
were assigned randomly to 1 of 4 groups: 1) actual tail snip, 2) sham tail snip, 3) actual ear notch, or 4) sham ear notch. Vocalizations during the treatments were recorded with an ultrasonic recorder. Most mice (65%; n = 55) demonstrated no vocal response to the potentially painful procedures.
More mice that received actual tail snips produced audible sounds (11 of 29 mice) than did those that underwent sham tail snips (0 of 30 mice). In addition, audible vocalizations occurred more frequently during ear notch procedures (8 of 26 mice) than during sham ear-notch manipulations (2
of 24 mice). For all 20 of the mice that produced ultrasonic vocalizations, these calls were accompanied by simultaneous audible components. We conclude that ultrasonic vocalizations do not provide any more information than do audible vocalizations for assessing responses to potentially painful
procedures. In addition, because many mice made no sound at all after a potentially painful stimulus, vocalizations generally are not good metrics of acute pain in laboratory mice. Alternatively, the lack of vocalizations in many of the mice may suggest that tail snipping and ear notching
are not particularly painful procedures for most of these mice.
Four combinations of drugs—ketamine–xylazine, ketamine–xylazine–acepromazine (KXA), ketamine–xylazine–buprenorphine, and ketamine–xylazine–carprofen—were compared for their ability to produce anesthesia in BALB/c mice. Induction
time, anesthetic duration, blood pressure, pulse rate, and time to recovery were recorded. The anesthesia induced by each anesthetic combination was assessed by using reflex responses to standardized stimuli. The KXA combination produced stable physiologic parameters and was associated with
the longest duration of anesthesia (40 ± 8 min); immobility was produced in all other groups (38 ± 5 min), but a surgical plane of anesthesia could not be confirmed. All anesthetic protocols produced significant hypotension. No deaths occurred. We recommend KXA as a safe and
reliable anesthetic for mice requiring a surgical plane of anesthesia.
Pasteurella multocida is a bacterial pathogen that can cause significant disease and subsequent effects on research activities involving rabbits. Although several vaccines have been tested under laboratory conditions, field trials of vaccines for the control of P. multocida
in rabbits are few. We used a potassium thiocyanate extract (PTE) produced from P. multocida serotype D:3,12,15 to vaccinate Pasteurella-free rabbits at their introduction into a colony having endemic infection with P. multocida serotype A:3. Groups of 15 rabbits were
vaccinated either SC or IN with 1.0 mg PTE once weekly for 3 wk. In addition a control group was sham-vaccinated IN with saline. After the last vaccine dose had been administered, rabbits were housed with the general colony of a facility with endemic pasteurellosis. Serum samples obtained
before and 5 and 24 wk after the first dose of vaccine were evaluated by ELISA for anti-PTE IgG. Rabbits were euthanized if found in poor clinical condition, and all remaining rabbits were euthanized 24 wk after initial vaccination. Clinical disease typical of P. multocida infection
was observed in 10 of 15 saline-vaccinated rabbits, 4 of 15 IN PTE-vaccinated rabbits, and 1 of 15 SC PTE-vaccinated rabbits. Bacterial culture of the nasopharynx at the time of necropsy was positive for P. multocida in 10 of 15 control rabbits, 5 of 15 IN PTE-vaccinated rabbits, and
1 of 15 SC PTE-vaccinated rabbits. Anti-PTE serum IgG activity had developed in both IN- and SC-vaccinated rabbits by 5 wk, with significantly lower activity by 24 wk after initial vaccination. IgG activity was significantly greater in rabbits vaccinated SC compared with controls or those
vaccinated IN. In summary, PTE can be used to stimulate protective immunity to a heterologous strain of P. multocida, with stronger immunity generated by SC than IN vaccination.
Echocardiographic imaging has become the primary tool to evaluate cardiac structure and function in human and veterinary medicine. The cynomolgus monkey (Macaca fascicularis) is a nonhuman primate species frequently used in biomedical research, particularly for the study of human
cardiovascular disease and toxicology, yet echocardiographic reference ranges are not available for this species. Using standard 2-dimensional and M-mode imaging, we performed echocardiographic evaluation of 118 female and 119 male cynomolgus monkeys under sedation with either ketamine hydrochloride
(10 mg/kg IM) alone or with a combination of tiletamine hydrochloride and zolazepam (4.0 mg/kg IM) and atropine sulfate (0.015 mg/kg IM). Reference ranges were developed (tolerance interval methodology) separately for each gender for heart rate, left ventricular (LV) size (interventricular
septum in diastole, LV internal diameter in diastole and systole, LV free wall in diastole), left atrial diameter, and aortic diameter. LV functional parameters (fractional shortening, aortic peak flow velocity, LV ejection time, and LV preejection period) and mitral valve E point to septal
separation were also measured. After normalization for body weight (1.7 to 6.3 kg), the data were analyzed for gender- and sedation-associated differences. Using a large number of healthy subjects (118 of each gender), we have developed gender-specific echocardiographic reference ranges for
cynomolgus monkeys.
Murine norovirus (MNV) is a common viral infection of mice in many research facilities. MNV infects hematopoietic cells and alters their cellular morphology. Because of MNV's probable effects on the systemic immune response of infected mice the decision was made to eradicate the virus
from 2 rooms containing infected animals in our vivarium. Two different eradication methods were selected. One room, in which most of the indirectly exposed sentinels had antibodies to MNV, was depopulated and thoroughly cleaned prior to repopulation. In the other room, in which only 13% of
the sentinels had positive MNV titers, selective testing was used, and MNV-positive animals were removed. Data from surveillance of the sentinel mice exposed to dirty bedding indicate that the test-and-removal method was ineffective in eliminating MNV from the room, whereas sentinel mice in
the room that underwent depopulation and cleaning prior to repopulation have not shown any evidence of MNV since December 2006.
Despite extensive guidelines and regulations that govern most aspects of rodent shipping, few data are available on the physical environment experienced by rodents during shipment. To document the thermal environment experienced by mice during air shipments, we recorded temperatures
at 1-min intervals throughout 103 routine interinstitutional shipments originating at our institution. We found that 49.5% of shipments were exposed to high temperatures (greater than 29.4°C), 14.6% to low temperatures (less than 7.2°C), and 61% to temperature variations of 11°C
or more. International shipments were more likely than domestic shipments to experience temperature extremes and large variations in temperature. Freight forwarders using passenger airlines rather than their own airplanes were more likely to have shipments that experienced temperature extremes
or variations. Temperature variations were most common during stopovers. Some airlines were more likely than others to experience inflight temperature extremes or swings. Most domestic shipments lasted at least 24 h, whereas international shipments lasted 48 to 72 h. Despite exposure to high
and low temperatures, animals in all but 1 shipment arrived alive. We suggest that simple measures, such as shipping at night during hot weather, provision of nesting material in shipping crates, and specifying aircraft cargo-hold temperatures that are suitable for rodents, could reduce temperature-induced
stress. Measures such as additional training for airport ground crews, as previously recommended by the American Veterinary Medical Association, could further reduce exposure of rodents to extreme ambient temperatures during airport stopovers.
As more emphasis is placed on enhancing the psychological well-being of nonhuman primates, many research facilities have started using positive reinforcement training (PRT) techniques to train primates to voluntarily participate in husbandry and research procedures. PRT increases the
animal's control over its environment and desensitizes the animal to stressful stimuli. Blood draw is a common husbandry and research procedure that can be particularly stressful for nonhuman primate subjects. Although studies have demonstrated that chimpanzees can be trained for in-cage venipuncture
using PRT only, fewer studies have demonstrated success using similar techniques to train macaques. It is often assumed that macaques cannot be trained in the same manner as apes. In this study, we compare PRT data from singly housed adult rhesus macaques (Macaca mulatta; n = 8) with
data from group-housed adult chimpanzees (Pan troglodytes; n = 4). All subjects were trained to place an arm in a 'blood sleeve' and remain stationary for venipuncture. Both facilities used similar PRT techniques. We were able to obtain repeated blood samples from 75% of the macaques
and all of the chimpanzees. The training time did not differ significantly between the 2 species. These data demonstrate that macaques can be trained for venipuncture in a manner similar to that used for chimpanzees.
A rhesus macaque (Macaca mulatta) infected with simian-human immunodeficiency virus (SHIV) while undergoing AIDS research, required a comprehensive physical examination when it presented with slight peripheral edema, hypoalbuminemia, and proteinuria. Many of the clinical findings
were consistent with nephrotic syndrome, which is an indication of glomerular disease, but the possibility of concurrent disease needed to be considered because lentiviral induced immune deficiency disease manifests multiple clinical syndromes. The animal was euthanized when its condition
deteriorated despite supportive care that included colloidal fluid therapy. Histopathology confirmed membranoproliferative glomerulonephritis, the result of immune complex deposition most likely due to chronic SHIV infection. Clinical symptoms associated with this histopathology in SHIV-infected
macaques have not previously been described. Here we offer suggestions for the medical management of this condition, which entails inhibition of the renin–angiotensin–aldosterone system and diet modifications.