The calming effect of stimuli presentation on infant Japanese Macaques (Macaca fuscata) under stress situation: a preliminary study

In human newborns, presentation of sounds and odors under stress situations had a calming effect on behavioral and cortisol responses (Kawakami et al., 1996, 1997). These calming effects were examined with 10-day- and 15-day-old Japanese macaques. In Study 1, white noise presentation (Experimental conditions) at the blood sampling was compared with no sound presentation (Control conditions) at the blood sampling. White noise presentation has a calming effect on coded behavioral responses. In Study 2, lavender scent presentation (Experimental conditions) at the blood sampling was compared with no odor presentation (Control conditions) at the blood sampling. Lavender presentation has a calming effect on cortisol responses in the marginal level. From the data of these studies, the salivary cortisol levels were related to the cortisol levels in plasma. Our results may suggest the different effects of sound and odor on infant Japanese macaques.     

Effects of single and multiple injections of ketamine hydrochloride on serum hormone concentrations in male cynomolgus monkeys

Using simulated short- and long-term effect studies, we evaluated the effect of ketamine anesthesia on serum cortisol, testosterone, and immunoreactive luteinizing hormone (ILH) and bioactive LH (BioLH) concentrations in adult male cynomolgus monkeys. Cortisol, testosterone, and ILH were measured by use of radioimmunoassay, and BioLH was measured by use of a radioreceptor assay method. For the acute effect, the first group (eight monkeys) was given four successive intramuscular injections of ketamine (10, 5, 5, and 5 mg/kg of body weight at 0, 30, 60, and 110 min respectively). Blood samples were taken at 0, 15, 30, 45, 60, and 120 min. For the long-term effect, the second group (10 monkeys) was given a single injection of ketamine (10 mg/kg) once a week for 4 consecutive weeks. Blood samples were taken 5 to 10 min after each injection, then were used to determine the variation in hormone concentrations among the monkeys (inter-individual variation) and within each monkey (intra-individual variation). There were no statistically significant differences in serum cortisol, testosterone, ILH, and BioLH values between the first blood sample (before the ketamine injection) and sequential blood samples in monkeys of the first group. Although intra-individual variation in the hormones (i.e., hormonal change within each monkey) was not statistically significant, inter-individual variation (among the monkeys) was significantly (0.00001 < P < 0.033) different in monkeys of the second group. These results indicate that an adequate number of animals must be used to minimize animal-to-animal variability. Our results confirm that ketamine is a suitable anesthetic agent to immobilize male cynomolgus monkeys in experimental studies (short- and long-term studies) aimed at elucidating hormonal changes.     

Baseline and stress levels of cortisol in conscious and unrestrained Japanese macaques (Macaca fuscata)

A vest and tethering system was applied to Japanese macaques (Macaca fuscata) to collect blood samples under less stressful conditions. The level of plasma cortisol was assayed to assess the amount of stress. The pattern of plasma cortisol fluctuation during 24 hours was consistent under non-stress conditions. The plasma cortisol level was increased significantly by encounter and venipuncture. The increase was especially noteworthy when the experimental macaques encountered a large adult male, reflecting the strong stress on macaques. As venipuncture is a common medical procedure, and the encounter between macaques who have never met before occurs frequently, this vest and tethering system is useful for the assessment of the amount of stress in the daily care of macaques in a laboratory.     

Effects of ketamine sedation on glucose clearance,insulin secretion and counterregulatory hormone production in baboons (Papio hamadryas)

Since the effects of ketamine sedation seem to differ between subspecies of baboons, we assessed the endocrine response to an intravenous glucose tolerance test (IVGTT) in 12 hamadryas baboons. The first phase insulin secretion, basal insulin, and glucose levels, as well as the glucose clearance, were significantly lower in sedated baboons as compared to fully awake animals. Glucagon and Cortisol were significantly higher, while growth hormone was lower during ketamine sedation. Papio hamadryas appears to be a promising pre-clinical model for the study of endocrine replacement therapy in insulin-dependent diabetes. However, the data obtained must be interpreted with the knowledge that the anesthetic employed to allow for testing of the animals does have an effect on the parameters described in this report.     

Effect of nasal instillation of female urine or vaginal exudate on serum cortisol and prolactin levels in isolated and anesthetized male rhesus monkeys (Macaca mulatta)

Two male adult rhesus monkeys were used and caged individually. The room was temperature-controlled having a light-dark period of 12/12 hours. The animals were rapidly immobilized and immediately anesthetized with ketamine i. m. (10 mg/kg of body weight). They were bled four times at 15, 30, 45 and 60 mins after the ketamine injection, twice a week for 6 weeks. When necessary, maintenance doses of ketamine were administered. The serum levels of cortisol and prolactin after nasal instillation of a suspension of vaginal exudate showed lower values than in control conditions (nasal instillation of saline). The control levels of cortisol tended to increase up to 60 mins, whilst in experimental conditions (nasal instillation of female urine or vaginal exudate) did not show such an increase. Cortisol remained similar during the sampling and similar to the 15 mins control levels, but the difference is statistically significant only after instillation of vaginal exudate as compared with control. The levels of prolactin did not show significant variations during sampling either in control or after female urine instillation. However, the instillation of vaginal exudate decreased the prolactin levels at 15 mins which tended to recover the control levels up to 60 mins. These results support the hypothesis, discussed in a previous paper, that some chemical information from females suppresses or mitigates the effect of acute stress resulting from handling the animals before anesthesia.     

Anesthesia in female white-tailed deer using Telazol and xylazine

Thirty two free-ranging female white-tailed deer (Odocoileus virginianus) were anesthesized with varying Telazol and xylazine HCl combinations in Front Royal (Virginia, USA) between August 1992 and September 1992. All animals were caught in baited box traps, manually restrained, and hand injected with a combination of Telazol and xylazine administered intramuscularly. Deer received mean +/- SE dosages of 2.53+/-0.16 mg/kg Telazol and 0.69+/-0.05 mg/kg of xylazine. These dosages achieved a rapid and effective anesthetic plane for short-term procedures such as weighing, blood collection, and translocation. Eight of 32 deer (25%) required an intravenous (i.v.) supplement of ketamine HCl (100 mg) to maintain a safe plane of anesthesia. Ketamine supplementation provided an average of 11.8+/-2.0 min additional safe handling. Satisfactory reversals were achieved in all deer by administering yohimbine HCl 16 mg i.v. (dose range, 0.22 to 0.48 mg/kg) to all animals.     

The efficacy of orally dosed ketamine and ketamine/medetomidine compared with intramuscular ketamine in rhesus macaques (Macaca mulatta) and the effects of dosing route on haematological stress markers

BACKGROUND: This study compared the efficacy of two orally-dosed (PO) anaesthetic regimens for chemical immobilization in rhesus macaques (Macaca mulatta), versus the standard protocol of intramuscular (TM) ketamine. In addition, the effects of dosing route on haematological stress markers were evaluated. METHODS: Testing was conducted on 18 chronically housed animals. Animals were trained to accept oral dosing and then randomly assigned to one of three drug regimens: (1) ketamine IM, (2) ketamine PO, (3) Ketamine/medetomidine PO. Sedation levels for each regimen were evaluated. RESULTS: Oral dosing alone was not sufficient to achieve a plane of sedation that allowed for safe handling. Serum cortisol and glucose levels were unchanged across groups, although differences were observed in the leukogram profiles. CONCLUSION: The oral dosages used in this study fell short in providing adequate sedation for safe handling for routine veterinary procedures. Leukogram profiles indicated that orally dosed animals experienced a higher level of stress.     

The baboon model under anesthesia for in vivo cerebral blood flow studies using single photon emission computed tomographic (SPECT) techniques.

Single photon emission computed tomography of the brain can be useful in animal experimentation directed toward cerebral conditions. A well established and understood baboon model, necessarily under anesthesia, could be especially valuable in such investigations. Six normal baboons were studied under various anesthetic agents and their combinations: ketamine, thiopentone, pentobarbitone, and halothane. Cerebral blood flow (CBF) studies were performed with 99mTc-HMPAO. CBF effects from various anesthesia were detected, requiring careful choice of the anesthesia for cerebral investigations.     

Immobilization of Chacoan peccaries (Catagonus wagneri) using medetomidine, Telazol, and ketamine

A combination of medetomidine, Telazol, and ketamine hydrochloride was used to immobilize captive Chacoan peccaries (Catagonus wagneri) for translocation within Paraguay during August-October 2002. Animals were darted in enclosed areas of varying size. The average dose used was 32.5+/-7.2 microg/kg of medetomidine, 0.63+/-0.2 mg/kg of Telazol, and 3.9+/-0.65 mg/kg of ketamine. First effects were noted at 4.3+/-2.1 min, and ability to handle the animals was achieved by 12.6+/-3.7 min. Heart and respiratory rates declined and oxygen saturation increased during anesthesia. Muscle relaxation was good. Atipamezole was used to antagonize the medetomidine, although recoveries were still slow. This drug combination provided adequate immobilization of Chacoan peccaries; however, this protocol would not be considered to be reversible, and confinement during recovery is recommended.     

外科教学中犬的复合麻醉效果观察

目的比较氯胺酮、地西泮和丙泊酚复合麻醉在外科教学中对犬的麻醉效果。方法成年健康杂种犬42条,诱导麻醉相同,均肌注氯胺酮（10 mg/kg）和氟哌利多（0.5 mg/kg）混合液。静脉维持采用不用的方法,分为三组,分别是静脉滴注氯胺酮地西泮混合液（n=12）、静脉推注氯胺酮地西泮混合液（n=12）和静脉滴注丙泊酚利多卡因混合液（n=18）。结果三组麻醉效果显示,静脉滴注丙泊酚利多卡因混合液效果最好,优83.3%,良16.7%,死亡率0%。结论在外科教学中,对犬采用丙泊酚复合麻醉是一种较为理想的麻醉方法。     

Abstracts of papers to be presented at the Tenth Annual Meeting of the American Society of Primatologists Madison,Wisconsin June 13–16, 1987

Invasive surgical procedures are often used to study the reproductive and adrenocortical endocrine systems in primates. Anesthetic agents must, therefore, be used that have the least confounding effects on these systems. The present study was designed to characterize various adrenocortical endocrine responses of female baboons (Papio anubis), each treated for 120 minutes with an infusion of ketamine HCl (6 mg/min) in 5% dextrose in water (0.40 ml/min), a combination of ketamine and acetylpromazine (0.6 mg acetylpromazine and 6 mg ketamine HCl/min) in 5% dextrose in water, or inhalation of vaporized halothane (1.0% halothane, N₂O 25%, 1 liter/min; O₂ 75%, 3 liters/min). Blood samples were collected throughout the treatment period, and serum was assayed for prolactin (PRL), dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and cortisol (F). No significant elevations in DHA, F, or PRL concentrations were found following infusion of ketamine alone. Only serum DHAS concentrations were significantly altered after long-term exposure to ketamine. Acetylpromazine increased PRL concentrations tenfold to levels significantly greater than those in ketamine- and halothane-treated animals but had no effect on serum DHA, DHAS, or F. Treatment with halothane had no effect on serum PRL, DHA, or DHAS but did suppress F (>40%) concentrations over time. These data indicate that ketamine is best suited for the collection of biological samples when deep analgesia is not required but that halothane is preferable in the latter situation.     

Effect of ketamine anesthesia on daily food intake in Macaca mulatta and Cercopithecus aethiops

Ketamine hydrochloride is frequently administered to non-human primates as a means of chemical restraint. This procedure can be a frequent source of stress to monkeys at research facilities, impacting animal health, well-being and research quality. This study was designed to measure ketamine's effect on daily food intake, a parameter that reflects and influences animal well-being and directly impacts research studies. On five occasions, baseline daily food intake was compared to daily food intake occurring 24, 48, 72, 96, and 120 h after an intramuscular injection of 10 mg/kg ketamine in male African green monkeys (AGMs) (Cercopithecus aethiops) and male and female rhesus macaques (Macaca mulatta). AGMs and female rhesus macaques had significantly reduced daily food intake during the first 4 days after receiving ketamine. The AGMs continued to display significantly reduced daily food intake on the fifth day after ketamine. The male rhesus macagues showed a trend toward reduced daily food intake, greatest during the first 2 days and remaining less than baseline intake through the fifth day following ketamine. The degree of observed food intake reduction was most severe at the 24 h (mean percent intake reduction: AGMs: 57%; rhesus males: 48%; rhesus females: 40%) and 48 h time points (AGMs: 24%; rhesus males: 14%; rhesus females: 13%). A subset of the AGMs that did not receive ketamine, but observed other animals in the room receive ketamine, showed reduced food intake at 24 and 48 h after ketamine, though not to the degree associated with ketamine administration. These results indicate that ketamine anesthesia is associated with a prolonged reduction in daily food intake in AGMs and rhesus macaques. Frequent use of ketamine in non-human primates may have a significant impact on animal health and well-being, and alternatives to its use warrant consideration.     

Anesthetic and nephrotoxic effects of Telazol in New Zealand white rabbits.

Telazol was evaluated as an anesthetic for rabbits. Two groups of five rabbits each were injected intramuscularly with 32 or 64 mg/kg of Telazol, and the depth and duration of anesthesia period monitored. At both doses, the righting reflex was lost within 2 minutes postinjection. Animals in both groups responded to noxious stimuli for the duration of the anesthesia. Hematology and urinalyses were performed daily for 7 days postinjection. Hematologic parameters remained unchanged in both groups. In the high-dose group, blood urea nitrogen and serum creatinine levels increased 1 day postinjection and continued steadily throughout the week. Elevations in urine protein and the presence of casts correlated with this increase. In the low-dose group, blood urea nitrogen and creatinine levels increased and protein was present in the urine of four of five rabbits beginning approximately 5 days postinjection. Histologically, severe renal tubular necrosis was evident 7 days postinjection in all high-dose rabbits and in three rabbits in the low-dose group. Our results indicate that Telazol does not produce analgesia in rabbits and is nephrotoxic at both 32 and 64 mg/kg. We conclude that Telazol is contraindicated for use in rabbits.     

The effects of handling and anesthetic agents on the stress response and carbohydrate metabolism in northern elephant seals

Free-ranging animals often cope with fluctuating environmental conditions such as weather, food availability, predation risk, the requirements of breeding, and the influence of anthropogenic factors. Consequently, researchers are increasingly measuring stress markers, especially glucocorticoids, to understand stress, disturbance, and population health. Studying free-ranging animals, however, comes with numerous difficulties posed by environmental conditions and the particular characteristics of study species. Performing measurements under either physical restraint or chemical sedation may affect the physiological variable under investigation and lead to values that may not reflect the standard functional state of the animal. This study measured the stress response resulting from different handling conditions in northern elephant seals and any ensuing influences on carbohydrate metabolism. Endogenous glucose production (EGP) was measured using [6-(3)H]glucose and plasma cortisol concentration was measured from blood samples drawn during three-hour measurement intervals. These measurements were conducted in weanlings and yearlings with and without the use of chemical sedatives--under chemical sedation, physical restraint, or unrestrained. We compared these findings with measurements in adult seals sedated in the field. The method of handling had a significant influence on the stress response and carbohydrate metabolism. Physically restrained weanlings and yearlings transported to the lab had increased concentrations of circulating cortisol (F(11, 46)?=?25.2, p<0.01) and epinephrine (F(3, 12)?=?5.8, p?=?0.01). Physical restraint led to increased EGP (t?=?3.1, p?=?0.04) and elevated plasma glucose levels (t?=?8.2, p<0.01). Animals chemically sedated in the field typically did not exhibit a cortisol stress response. The combination of anesthetic agents (Telazol, ketamine, and diazepam) used in this study appeared to alleviate a cortisol stress response due to handling in the field without altering carbohydrate metabolism. Measures of hormone concentrations and metabolism made under these conditions are more likely to reflect basal values.     

The effects of ketamine anesthesia on hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis)

The effects of ketamine anesthesia (15 mg/kg body weight) on hematological and serum biochemical values were examined in six female cynomolgus monkeys (Macaca fascicularis) who were born in the wild. As control, another six female cynomolgus monkeys of the same origin were injected with physiological saline. The white blood cell count, total protein concentration, albumin concentration and calcium concentration decreased after the injection of ketamine, whereas the red blood cell count, hematocrit value, hemoglobin concentration, total cholesterol concentration, free cholesterol concentration, triglyceride concentration, transaminase activities (GOT, GPT) and alkaline phosphatase activity were not affected. A transient increase of the serum glucose level was observed within 10 minutes after ketamine injection. The relationship between these effects of ketamine anesthesia and serum cortisol levels measured by radioimmunoassay was discussed.     

Effect of nembutal on LH release in baboons.

Regularly cycling female baboons were selected and maintained under a diurnal light schedule from 0500 to 1900 hr (CST). Beginning three days prior to the expected LH peak, blood was collected daily at 0800 and 1600 hr for 6 days in 5 baboons under light sedation for radioimmunoassay of plasma LH and estrogen. The plasma level of LH increased linearly and reached a peak in the afternoon of the second day. The peak in plasma estrogen appeared prior to the LH peak. In order to examine the critical period of LH surge in baboons, nembutal was injected daily at 1300 hr beginning a few days prior to expected LH relase. Initial dose of nembutal was 35 mg/kg body weight, but a supplementary dose was later required for a full 5 hours of anesthesia. Blood was collected at 1600 hr from 4 baboons during nembutal injections and after cessation of nembutal injections for radioimmunoassay of plasma LH and estrogen. It was found that nembutal injections suppressed LH release in 2 baboons, and caused a delay of LH release in 2 baboons. However, the plasma level of estrogen declined immediately after initiation of nembutal injection and remained lower. The evidence illustrates the nature of the neural components of LH release which became effective in the afternoon during the ovulatory phase. In addition, a linear increase in plasma level of LH, which is due to accumulation of circulating LH, is necessary for induction of ovulation in baboons.     

雄性短尾猴维持临时配偶关系的行为适应性

临时配偶关系指多雌多雄灵长类群体中的一只成年雄性连续跟随一只成年发情期/性接受期的雌性形成的异性关系,在季节性繁殖物种的交配季节表现的尤为明显,是雄性个体提高交配成功的策略之一。为了探讨能量消耗对这种行为的约束,本研究于2017年8月至2018年1月,以栖息于安徽黄山的短尾猴鱼鳞坑A1群（YA1群）的8~10只成年雄性为研究对象,采用目标动物取样法、行为取样法以及全事件记录法采集成年雄性自然发生的行为数据。通过分析移动时间、觅食时间和交配频次等行为指标,同时测定作为个体能量状态生理指标的尿液C-肽浓度（Urinary C-peptide , UCP）,从行为和生理两个方面研究雄性短尾猴维持临时配偶关系的适应性特征。研究期间,在临时配偶期内,雄性的移动时间无显著变化,但觅食时间和交配频率显著增加;在临时配偶期内,当存在雄性竞争者时,雄性的觅食时间显著减少;临时配偶关系对雄性的UCP水平无显著影响。结果表明,雄性短尾猴在临时配偶期内可能会根据能量消耗的情况以及守护雌性周围的社会环境对自身行为进行调整,以减少其在临时配偶期内的能量投资,提高自身维持临时配偶关系的行为适应性。     

氯胺酮对川金丝猴的麻醉效应

本研究单独使用氯胺酮对24只神农架川金丝猴（Rhinopithecus roxellana）进行麻醉,比较其在诱导期、麻醉期及恢复期的持续时间和行为反应差异,探讨氯胺酮对不同性别、不同年龄川金丝猴的麻醉效果。结果显示：24例受试动物注射氯胺酮（剂量5.90-15.71mg/kg）后,镇痛、镇静和肌松效果良好,无意外死亡。其中,诱导期表现四肢逐渐无力,流涎,身体逐渐倒下,偶有嘴空嚼;麻醉期表现肌松良好,呼吸通畅,伴有嘴空嚼;恢复期表现以手指和躯干振动,开始恢复意识,嘴空嚼情况增多,尝试坐立和行走,最后恢复正常;诱导期、麻醉期和恢复期持续平均持续时间分别为(4.00 ± 1.77)min、(21.67 ± 5.03)min和(31.79 ± 6.07)min。本研究首次监测到川金丝猴在麻醉过程中出现嘴空嚼行为（没有进食的情况下嘴上下及左右咀嚼）。数据分析表明,在麻醉过程中雄性个体恢复期时长明显大于雌性,雄性个体在恢复期空嚼行为的次数明显小于雌性;而性别对诱导期、麻醉期,年龄对诱导期、麻醉期和恢复期的时长及行为影响均无明显差异。     

Effects of ketamine on the dynorphin levels and the ethylketocyclazocine (EKC) receptor binding in discrete regions of rat brains

Intraperitoneal (ip) injection of ketamine increased the concentration of dynorphin in the cortex of rat brain, while decreased it in the septal area. The affinity of ethylketocyclazocine (EKC) receptor binding was decreased in the cortex, but increased in the septal area after pretreating the rats with ketamine. This suggests that the dynorphin neuronal system is stimulated in the cortex and suppressed in the septal area by ketamine. In other 5 brain areas, ketamine had no effect on neither dynorphin concentration nor EKC receptor binding. As dynorphin was reported to produce seizure and spike discharge in the cortex while suppressed the hippocampal EEG of rat brain, it is likely that the dynorphin neuronal system may play at least a part in ketamine induced electrophysiological changes in the brain.     

Response of wild subantarctic fur seal (Arctocephalus tropicalis) females to ketamine and tiletamine-zolazepam anesthesia

This study is the first to compare the anesthetic effects of two cyclohexamines on free-ranging subantarctic fur seal (Arctocephalus tropicalis) females. From April to July 1999, 107 females were immobilized for tooth extraction and blood sampling, using either ketamine (Ketalar, n = 58) alone or tiletamine-zolazepam (Zoletil 100, n = 49) mixture. Animals were injected intramuscularly at mean doses of 2.1 mg/kg for ketamine and 1.1 mg/kg for tiletamine-zolazepam mixture. Individual response to both drugs was highly variable. The dosage required to achieve a satisfactory level of anesthesia was smaller for subantarctic fur seals than for most other species of seals and was less for animals in better body condition. Few side effects were observed during the trials, aside from mild tremors caused by ketamine, and respiratory depression or prolonged apnea caused by tiletamine-zolazepam. We recommend use of ketamine, especially by those with little experience in anesthesia of fur seals. However, precautionary measures should be taken, such as using low doses for animals in good body condition and being prepared for anesthetic emergencies to avoid any casualties.