Physicians and veterinarians often prescribe oxytocin to treat dystocia. However, oxytocin administration to pregnant women or animals is not without risk. In the venue of laboratory animal medicine, the use of oxytocin may present confounding variables to research. Although oxytocin has been studied extensively, many of its physiologic effects and interactions with other hormones remain unclear. Investigator concerns about adverse and confounding effects of oxytocin in their research mice prompted the current review of oxytocin and its use to treat murine dystocia. Well-controlled studies of oxytocin in dystocic mice have not been conducted. However, in humans and other animals, inconsistent and adverse effects are well-documented. Limited knowledge of the complex physiologic and molecular mechanisms of action of oxytocin and scant support for the efficacy of oxytocin in dystocic mice fail to meet the standards of evidence-based veterinary medical practice. The administration of oxytocin is contraindicated in many cases of dystocia in research mice, and its use in dystocic mice may be unfounded. A brief review of oxytocin and the physiologic mechanisms of parturition are provided to support this conclusion. Alternative treatments for murine dystocia are discussed, and a holistic approach is advocated to better serve animal welfare and to safeguard the integrity of valuable research. Laboratory animal veterinarians overseeing the development of guidelines or standard operating procedures for technician or investigator treatment of dystocic mice should understand the effects of oxytocin administration in light of relevant research.

The goal of environmental enrichment for laboratory animals is to improve welfare, but some enrichment practices may affect research in unintended ways or even be harmful to the animals themselves. We previously found that mice raised at a commercial vendor then given multiple enrichment devices upon arrival at our facilities experienced thymic atrophy and greater variation in measured parameters than did their unenriched counterparts, suggesting that enrichment conditions affected corticosteroid expression in mice. The current study verified and expanded these results, examining 120 female BALB/c mice raised with or without nesting material at a commercial vendor (n = 60 per group) and allocated (n = 20 per group) to receive no enrichment, nesting material, or 'superenrichment' on arrival at our facilities. Nesting material provided prior to weaning was associated with higher levels of urinary corticosteroid, whereas superenrichment and nesting material during the adult period both led to increased thymic atrophy. Paradoxically, mice that never received enrichment, despite having the lowest corticosterone levels and least thymic atrophy, had increased tail wounds resulting from aggressive interactions. Therefore, enrichment devices that are as seemingly innocuous as nesting material, even if only provided in the preweaning period, may lead to significant, lasting changes in behavioral, physical, or immunologic measures with the potential to alter research outcomes.

The effect of chronic daily orogastric gavage with water (5 mL/kg) on behavior and physiology was evaluated in male Sprague–Dawley rats. Treatment groups included: unmanipulated control, restraint control, dry gavage, and gavage, with all rats singly housed (n = 9 or 10 per group). In addition, a group of pair-housed rats (n = 18) was included to determine whether social housing affected response to gavage. Weekly body weights and food consumption were recorded as well as use of a nylon chew toy for enrichment. Feces were collected biweekly at the end of the light and dark phases for fecal corticoid metabolite determinations. After 28 d of treatment, animals underwent conditioned place preference testing to evaluate sensitivity to motivational properties of the anxiolytic drug chlordiazepoxide (5.6 mg/kg SC). Brain and paired adrenal gland weights were collected at necropsy. Week 2 total fecal corticosterone levels were elevated in all groups and attributed to a fire alarm accidentally tripped during building renovations. No differences occurred in body weight or food consumption between any groups. All groups used a nylon chew toy given for enrichment and demonstrated mild preference for the drug-associated chamber. Fecal weights and corticoid metabolite levels were similar between all groups at week 4 and showed normal diurnal variation. No biologically significant variations were noted in brain or paired adrenal gland to body weight ratios. We conclude that orogastric gavage of aqueous solutions at 5 mL/kg does not negatively affect the welfare of laboratory rats acclimated to handling.

Body condition scoring (BCS) is a subjective semiquantitative method of assessing body fat and muscle. Scoring systems use a scale in which the midrange represents optimal body condition, lower values represent lean to emaciated conditions, and higher values indicate excessive body fat. A valid BCS system is clearly described, relevant to the species, shows agreement within and between raters, and is consistent with objective measures. The goal of the current study was to assess intra- and interrater variability of a BCS system that uses a 1-to-5 scale and entails the palpation of key anatomic sites (hips, spine, pelvis, thorax, and abdomen) to assess prominence of bony structures, muscle mass, and subcutaneous fat. To assess interrater variability, 4 raters independently assessed BCS in 616 rhesus macaques (Macaca mulatta) in 4 age groups: infant, younger than 1 y; juvenile, 1 to 4 y; subadult, 4 to 7 y; and adult, 7 to 17 y. To assess intrarater variability, each rater independently reevaluated a subset of adult macaques (n = 15) within 2 wk of initial evaluation. A weighted κ score was used to analyze intra- and interrater variability. Agreement between raters was highest for subadult and adult macaques, intermediate for juveniles, and least for infants. Intrarater agreement was high for all raters except one, for which it was moderate. Our results suggest that raters applied the BCS system most consistently to adult and subadult macaques and less so to juvenile and infant animals. However, the percentage agreement between raters to within one half of a score unit increased markedly when raters scored infants in the context of 'as is' rather than 'ideal for age.'

Most mice used in research are purchased devoid of specific pathogens. Experimental studies required us to evaluate the profile of infective agents harbored in mice sold as pets or food for captive reptiles. Anecdotal reports regarding disease in these mice abound, but there are few published reports on disease prevalence. Purchasers are unaware of the potential zoonotic or adventitious infections carried by these mice. This survey investigated the prevalence of ectoparasites, endoparasites, and viral, bacterial, and fungal agents carried by apparently healthy mice (n = 18) obtained from 6 pet stores in New York City, with an emphasis on those pathogens with zoonotic potential. Serology revealed the presence of antibodies to numerous murine specific viral agents in most mice tested. Ectoparasites were present on most mice. Examination of intestinal contents revealed nematode and cestode parasites, including a potential cause of human cestodiasis, Rodentolepis nana. A multidrug-resistant β-hemolytic Enterococcus faecium was isolated from the skin of mice from a single pet store; this organism causes community-acquired infections in humans. This study confirms that pet-store mice are exposed to or carry numerous pathogens that are excluded from laboratory rodent colonies. The potential for laboratory animal personnel to serve as mechanical vectors of unwanted infective agents likely is increased when these persons handle pet-store mice at home.

Postoperative pain management in animals is complicated greatly by the inability to recognize pain. As a result, the choice of analgesics and their doses has been based on extrapolation from greatly differing pain models or the use of measures with unclear relevance to pain. We recently developed the Mouse Grimace Scale (MGS), a facial-expression–based pain coding system adapted directly from scales used in nonverbal human populations. The MGS has shown to be a reliable, highly accurate measure of spontaneous pain of moderate duration, and therefore is particularly useful in the quantification of postoperative pain. In the present study, we quantified the relative intensity and duration of postoperative pain after a sham ventral ovariectomy (laparotomy) in outbred mice. In addition, we compiled dose–response data for 4 commonly used analgesics: buprenorphine, carprofen, ketoprofen, and acetaminophen. We found that postoperative pain in mice, as defined by facial grimacing, lasts for 36 to 48 h, and appears to show relative exacerbation during the early dark (active) photophase. We find that buprenorphine was highly effective in inhibiting postoperative pain-induced facial grimacing in mice at doses equal to or lower than current recommendations, that carprofen and ketoprofen are effective only at doses markedly higher than those currently recommended, and that acetaminophen was ineffective at any dose used. We suggest the revision of practices for postoperative pain management in mice in light of these findings.

CO₂ administration is a common euthanasia method for research mice, yet questions remain regarding whether CO₂ euthanasia is associated with pain and stress. Here we assessed whether premedication with acepromazine, midazolam, or anesthetic induction with isoflurane altered behavioral and physiologic parameters that may reflect pain or stress during CO₂ euthanasia. Mice were assigned to 1 of 6 euthanasia groups: CO₂ only at a flow rate of 1.2 L/min which displaces 20% of the cage volume per minute (V/min; control group); premedication with acepromazine (5 mg/kg), midazolam (5 mg/kg), or saline followed by 20% V/min CO₂; induction with 5% isoflurane followed by greater than 100% V/min CO₂ (>6L/min); and 100% V/min CO₂ only (6 L/min). Measures included ultrasonic sound recordings, behavioral analysis of video record- ings, plasma ACTH and corticosterone levels immediately after euthanasia, and quantification of c-fos from brain tissue. Compared with 20% V/min CO₂ alone, premedication with acepromazine or midazolam did not significantly alter behavior but did induce significantly higher c-fos expression in the brain. Furthermore, the use of isoflurane induction prior to CO₂ euthanasia significantly increased both behavioral and neuromolecular signs of stress. The data indicate that compared with other modalities, 20% V/min CO₂ alone resulted in the least evidence of stress in mice and therefore was the most humane euthanasia method identified in the current study.

Remifentanil is a potent synthetic opioid with sedative effects. Intravenous remifentanil provides deep sedation and analgesia in laboratory animals during experimental procedures. We hypothesized that remifentanil would provide effective analgosedation during assisted mechanical ventilation without affecting respiratory mechanics in rats. Five male Sprague– Dawley rats (weight, 400 to 450 g) were assigned to receive assisted mechanical ventilation with continuous positive airway pressure for 5 h. Remifentanil (0.4 μg/kg/min IV) was delivered for the duration of ventilation. There were no differences between baseline, 1 h, and 5 h of ventilation in the mean arterial pressure, cardiac output, heart rate, and body temperature of all rats. Similarly, no differences were observed in the tidal volume, respiratory rate and minute ventilation, and gas exchange was equal in all rats at all time points. Frequent assessment of sedation by toe pinch documented loss of the pedal withdrawal reflex in all rats. We conclude that continuous remifentanil infusion provides sufficient analgosedation for mechanically ventilated rats without compromising hemodynamics, respiratory function, or gas exchange.

A valid and reliable scale for assessing level of sedation would facilitate appropriate sedation management in a porcine intensive care unit (ICU) model. The Richmond Agitation–Sedation Scale (RASS) is used often for human ICU patients. The purpose of this study was to estimate the content validity of the modified RASS for use in sedated, mechanically ventilated swine. The modified RASS includes descriptors specific for swine. A content validity assessment form was developed with 4 items and 5 response choices to assess the modified RASS for relevancy, sufficiency, clarity, and representativeness. The modified RASS and content validity assessment form were emailed to 23 veterinarians with experience in the care of swine or other large animals; participants judged the extent to which the modified RASS is valid for assessing sedation in mechanically ventilated critically ill swine. The criterion for acceptable validity evidence was a content validity index (CVI) of 0.80 or greater. Eight (67%) of 12 veterinarians who responded to the invitation to participate completed the assessment form. The item CVI varied from 0.50 to 0.88; scale CVI was 0.66. Because these values did not meet the a priori criterion, we concluded that the modified RASS does not have sufficient evidence of content validity for use with swine. The reliability of the modified RASS will be tested in the porcine ICU model, and experience with its use in swine will inform refinement of the scale descriptors for repeat assessment of content validity.

Recognition of pain and stress is a common challenge when working with laboratory mice. The aim of the current study was to identify noninvasive parameters to assess the severity and duration of possible pain and stress after vasectomy in BALB/c mice. Mice underwent isoflurane anesthesia with or without vasectomy. Body weight, food and water intake, and fecal corticosterone metabolites (FCM) were measured 3 d before and 3 d after the procedure. Behavior was recorded 1, 2, 4, and 8 h after the procedure. Food and water consumption and defecation were reduced postoperatively in the vasectomized group compared with mice given anesthesia only. FCM were elevated the first day after anesthesia in the control mice but not in the vasectomized group. Vasectomy resulted in behavioral changes that were not seen in the group that was anesthetized only. In conclusion, food and water consumption and pain-related behaviors, but not FCM, may be useful as noninvasive parameters to assess postoperative pain and stress in vasectomized mice.

The rat spinal-cord–injury (SCI) model is widely used to study the pathologic mechanisms that contribute to sensory and motor dysfunction in humans. This model is thought to mimic many of the negative outcomes experienced by humans after spinal contusion injury. We theorized that manual bladder expression contributed to the kidney and bladder lesions reported in previous studies using the rat SCI model. In the present study, rats were surgically implanted with bladder catheters after spinal contusion injury to provide continuous drainage of urine. After 72 h, the rats were euthanized and their kidneys and bladders examined histologically. BUN, serum creatinine, and urine protein were compared at 0 and 72 h after surgery. Kidney and bladder lesions were similar in SCI rats with and without implanted bladder catheters. BUN at 72 h was higher than baseline values in both groups, whereas serum creatinine was higher at 72 h compared with baseline values only in the catheterized rats. These findings indicate that suprapubic bladder catheterization does not reduce hydronephrosis in SCI rats and that the standard of care for bladder evacuation should continue to be manual expression of urine.

Intracoelomic (IC) injection of xylazine was evaluated as a chemical euthanasia method for Anolis lizards (Anolis carolinensis or Anolis distichus). Lizards were allocated into 5 groups of 10 animals each. Each group was euthanized by one of these methods: 10 mg xylazine (100 mg/mL) IC; 10 mg xylazine and 0.5 mg acepromazine (10 mg/mL) IC; 10 mg xylazine IC followed by intracardiac injection of 0.1 mEq KCl (2 mEq/mL) once heart beats were no longer discernable by Doppler; 500 mg/kg 1% NaCO₃-buffered MS222 solution IC followed by IC injection of 0.1 mL unbuffered 50% (v/v) MS222 solution (experimental groups); and 1.95 mg sodium pentobarbital, diluted 1:10 in sterile water (38.9 mg/mL) given IC (control group). Compared with those given sodium pentobarbital or MS222, lizards euthanized by using xylazine showed prolonged persistence of purposeful movement after cardiac arrest. Therefore, xylazine is not an acceptable alternative euthanasia agent for use in anoles.

Body condition scoring (BCS) is a subjective semiquantitative method of assessing body fat and muscle by palpation of key anatomic features. A previously published BCS system for rhesus macaques (Macaca mulatta) uses a scale comprising both whole and half units, in which the midrange represents optimal body condition (3.0), lower values represent emaciated to lean conditions (1.0 to 2.0), and higher values (4.0 to 5.0) indicate excessive body fat. A valid BCS system is well described, relevant to the species, has agreement within and between raters, and is consistent with objective measures. Here we correlate the subjective BCS assigned during physical exam with percentage body fat as determined by dual-energy X-ray absorptiometry (DEXA). Adult rhesus monkeys from an indoor-housed breeding colony were evaluated by the veterinary staff and assigned to 1 of 9 BCS score groups to give a minimum of 6 animals in each group. DEXA was used to obtain objective body composition measurements for macaques in each BCS group. Animals in the 'optimal' BCS group (3.0) had 25% body fat on average. Each full unit change in BCS was associated with an approximate 10% change in body fat percentage for macaques in the 2.0-to-5.0 BCS range. Absolute body fat in animals with BCS of 1.0 or 1.5 may be too low for accurate assessment by DEXA.

Thromboelastography is a clinical laboratory test used to assess global hemostasis. With technologic advances and the test's reemergence in human medicine, its utility in veterinary medicine is being explored. Because assays for PT, aPTT, and d-dimers require platelet-poor plasma, whereas thromboelastography is performed on whole blood, thromboelastography provides a more accurate representation of coagulation and allows the identification of hypocoagulable, hypercoagulable, and hyperfibrinolytic states. Conflicting information has been reported about the effects of age and sex on thromboelastog- raphy in humans and animals. Human studies have reported significant effects of age and sex on thromboelastography more often than have animal studies, but few publications are available about thromboelastography in the nonhuman primate and laboratory animal literature. We used a sample of 50 pigtail macaques (Macaca nemestrina) to determine whether age or sex influence thromboelastography values. Of 5 measured and 2 calculated variables produced by thromboelastography, sex had a significant effect only on the lysis-30 parameter, which also showed significant interaction between age and sex; values increased with age in male macaques but decreased with age in female macaques. In addition, we used the data to define reference intervals for thromboelastography parameters in pigtail macaques.