Pigtail Monkeys Research Articles

Social environment and nocturnal sleep: studies in peer-reared monkeys.

Nocturnal sleep was recorded for a total of 40 nights by means of totally implantable, multichannel biotelemetry from 11 peer-reared pigtail (Macaca nemestrina) monkey infants (aged 221 +/- 28 days). Fourteen sleep variables were compared to values previously obtained from similar-aged, mother-reared infants living in social groups. Sleep in peer-reared monkeys was more fragmented, contained less drowsy, more stage 2, less REM, fewer REM periods, and longer interREM intervals than sleep in mother-reared infants. It would appear that these effects are not due to a relatively impoverished environment that may accompany peer rearing, as has been reported to be true for rodents, but rather to the disruptive influence of sleeping with a peer in the absence of the organization and control effected by a monkey mother and a social group.

Yawning, scratching, and protruded lips: Differential conditionability of natural acts in pigtail monkeys (Macaca nemestrina)

Food rewards were given contingent upon the performance of one of three natural responses in adult male pigtail macaques: scratching, yawning, and the facial expression “protruded lips.” Scratching rapidly increased in frequency when it was followed by food, as did variability in form of scratching and one form in particular, using the feet. The facial expression was resistant to the conditioning procedures. Yawning increased in frequency when followed by food, with extinction and reconditioning procedures confirming the establishment of the conditioned response. This is the first report of the conditioning of yawning in primates. Together, the results contribute to the literature on the differential conditionability of different classes of behavior, and suggest the possibility that macaques can voluntarily display “reflexive” acts for social goals.

2 - The Efficacy of Acupuncture in Reversing the Unstable Bladder in Pig-Tailed Monkeys

2 - The Efficacy of Acupuncture in Reversing the Unstable Bladder in Pig-Tailed Monkeys

Lidoflazine does not improve neurologic outcome when administered after complete cerebral ischemia in primates.

In order to investigate the effects of the calcium entry blocker lidoflazine on neurologic outcome in primates following an episode of global brain ischemia, 12 pigtail monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia, followed by 48 h of intensive care treatment and daily neurologic evaluations for 96 h. The monkeys were randomly assigned to receive, in a blind fashion, either lidoflazine 1.0 mg/kg (n = 6) or inactive lidoflazine solvent (n = 6) at 5 min, 8 h, and 16 h postischemia. One monkey in the lidoflazine group did not meet preestablished protocol criteria and was excluded from data analysis. The remaining monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome was not significantly different between the lidoflazine- and placebo-treated groups (p greater than 0.5). No monkey in either group achieved a normal neurologic exam by 96 h postischemia. Three lidoflazine-treated monkeys and two placebo-treated monkeys died prior to the 96-h neurologic evaluation. These deaths were judged to be neurologic in origin. The authors concluded that lidoflazine does not improve neurologic outcome in primates when administered after 17 min of complete cerebral ischemia.

Excessive ovarian follicular development in pregnant pigtailed macaques (Macaca nemestrina).

To evaluate the status and possible control of ovarian follicular development during pregnancy, circulating levels of estrone (E1), estradiol-17β (E2), and follicle-stimulating hormone (FSH) were measured throughout gestation in both intact and ovariectomized pregnant pigtailed monkeys (Macaca nemestrina). From an additional group of pregnant monkeys, ovaries were obtained at late gestation (on day 150 or 159 of pregnancy) for histological studies. Circulating concentrations of E1 and E2 increased on day 13 and remained elevated for about 10 days; they then declined and reached low levels on day 32 of gestation. After day 60, there were gradual but smaller increases in estrogen levels to day 140, after which both E1 and E2 levels increased significantly, reaching maximum levels (E1 = 832.2 ± 210.8 pg/ ml; E2 = 1.66 ± 0.32 ng/ml) at the end of pregnancy. Removal of ovaries on day 35 of gestation did not affect pregnancy or the pattern of estrogen secretion. Serum concentrations of FSH demonstrated only minor fluctuations during pregnancy but were similar to those found during the early follicular phase of cycling pigtailed monkeys investigated in this study. Ovarian histology revealed extensive follicular growth; in addition to the corpus luteum of pregnancy, ovaries were packed with pre-antral, small antral, and medium-sized Graafian follicles. Some of these follicles appeared to be cystic and showed various degree of atresia; their general appearance was similar to the follicles of human females with polycystic ovary syndrome. Our data suggest that FSH may initiate ovarian follicular growth during gestation. High levels of estrogens were incapable of suppressing FSH secretion but may be responsible for the induction of atresia in a large number of follicles in pregnant pigtailed monkeys.

Infant abuse and neglect: Lessons from the primate laboratory

We review the several areas in which research on nonhuman primates contributes to our understanding of child abuse and neglect in human children. One special advantage of primate studies is that the experimental method can be utilized to examine the short- and long-term effects of relatively well-defined and circumscribed alterations in early experience and the manner in which they can affect later behavioral and physiological development. Four studies in M. nemestrina (pigtail) monkeys are described in which relatively short social separation experiences in infancy were associated with evidence of persistent changes in certain aspects of social behavioral functioning and immunological functioning, up to six years later, when the previously separated animals were in late adolescence or early adulthood. Such findings suggest that nonhuman primates may be used as animal model systems with considerable relevance to issues surrounding human child abuse and neglect.

The effects of dextrose infusion and head position on neurologic outcome after complete cerebral ischemia in primates: examination of a model.

The hypothesis that iv dextrose infusion prior to--and head position during--cerebral ischemia would influence the severity and pattern of neurologic injury was tested in primates. Fifteen pigtail monkeys weighing 3.3 +/- 0.2 kg (mean +/- SE) were subjected to 17 min complete cerebral ischemia followed by 24 h intensive care treatment and neurologic assessment for an additional 72 h. Monkeys were given 50 ml iv infusions of either dextrose 5% in 0.45% saline solution (n = 8) or lactated Ringer's solution (n = 7) during the preparatory period. This volume corresponds to approximately 1 1/70 kg individual. These same monkeys were placed in either the lateral (n = 3), prone (n = 5), or supine (n = 7) position during the ischemic period. Two monkeys failed to meet preestablished protocol criteria and were excluded from data analysis. Blood glucose immediately preischemia in the dextrose-treated group (181 +/- 19 mg X dl-1) was not significantly greater than in the group given lactated Ringer's solution (140 +/- 6 mg X dl-1; P = 0.07). Dextrose infusion resulted in significantly greater cerebral injury at 96 h postischemia when comparing both neurologic (P less than 0.05) and histopathology (P less than 0.05) scores. Specifically, dextrose administration resulted in the greatest injury to the insular cortex, thalamus, Purkinje cells, and substantia nigra. Although blood glucose was less than 250 mg X dl-1 in all monkeys at the time of complete cerebral ischemia, there was a high correlation between blood glucose rank and neurologic function rank (rs = 0.76; P less than 0.005). The authors were unable to note any effect of head position on the distribution of histopathologic lesions. Prior to removing the brain for histopathologic studies, four monkeys were given repeat infusions of 50 ml dextrose 5% in 0.45% saline solution over 11 +/- 1 min. These infusions produced increases in blood glucose from 56.7 +/- 7.6 to 244 +/- 24.9 mg X dl-1 (P less than 0.01) and increases in brain glucose from 1.64 +/- 0.22 to 5.11 +/- 0.48 mumol X g-1 (P less than 0.01).

Formula omitted][formula omitted] electrochemical recording of acetaminophen in non human primate brain

In vivo electrochemical recordings were obtained from the caudate nucleus of three young adult pigtail monkeys ( M. nemestrina ) following the oral administration of acetaminophen (APAP) (75 mg/kg). Using linear sweep voltammetry, electrodes in the right and left caudate were scanned alternately every five minutes. The electrochemical peak resulting from the APAP was monitored for at least 140 minutes following drug administration. Maximum APAP levels were detected in the monkey caudate 40 minutes following drug administration. Both right and left caudate displayed an identical time course, with oxidation potentials (E ox) similar on both sides of the brain. Blood samples were collected from one monkey by means of an intravenous catheter. Samples were obtained at approximately 5-minute intervals and over a period of 140 minutes following oral administration of APAP. Concentration of APAP in serum peaked 25 minutes after administration. In this animal the maximum electrochemical peak height was detected 40 minutes following APAP administration. These findings demonstrate the ability to measure APAP in the caudate nucleus of awake monkeys by means of electrochemical detection. This method may be useful for calibrating electrochemical electrodes in vivo , and it also provides a model system for studying drug kinetics in the brain.

Modulation of proteoglycan metabolism by aortic smooth muscle cells grown on collagen gels.

The nature of the extracellular matrix may influence the types and amounts of proteoglycans synthesized by arterial smooth muscle cells. To determine if collagen modulates proteoglycan metabolism by these cells, arterial smooth muscle cells derived from aortic explants of the pigtail monkey (Macaca nemestrina) were cultured on both tissue culture plastic and hydrated type I collagen gels for 7 days. Cells were radiolabeled with Na2[35S]O4 during the final 48 hours of the growth period, and proteoglycans were extracted from the culture medium and cell layer by using 4 M guanidine hydrochloride in the presence of protease inhibitors. Cultures on collagen accumulated approximately 40% less [35S]O4 = -radiolabeled proteoglycan when compared to cultures on plastic. However, cells on collagen accumulated approximately 50% of their newly synthesized proteoglycan within the cell layer, while cells on plastic deposited less than 20% of their total radiolabeled proteoglycan in this culture compartment. Pulse-chase analysis indicated that the elevated accumulation of proteoglycan observed in the cell layer of collagen cultures was due, at least in part, to inhibition of turnover of these molecules. Cells on both collagen and plastic synthesized a large chondroitin sulfate proteoglycan which was secreted into the medium and deposited within the cell layer. On the other hand, cells on collagen synthesized a smaller iduronic acid-rich dermatan sulfate proteoglycan which was deposited only within the collagen gel and not secreted into the medium. By comparison, cells grown on plastic synthesized both a small glucuronic acid-rich dermatan sulfate proteoglycan which was secreted into the medium as well as an iduronic acid-rich dermatan sulfate which was present in the cell layer. Unlike the cell layer-derived dermatan sulfate proteoglycan isolated from the collagen gels, the majority of the cell layer-derived dermatan sulfate from cells on plastic was insensitive to papain treatment and thus identified as free glycosaminoglycan chains. Analysis of the total radiolabeled proteoglycans isolated under the two culture conditions indicated that cultures grown on collagen accumulate less chondroitin sulfate proteoglycan and heparan sulfate proteoglycan but over twice as much iduronic acid-rich dermatan sulfate proteoglycan. This culture system is offered as a model to determine the mechanisms by which collagen may in part regulate the metabolism of proteoglycans by arterial smooth muscle cells.

Nucleotide sequence of the protease-coding region in an infectious DNA of simian retrovirus (STLV) of the HTLV-I family

A provirus clone of simian T-cell leukemia virus isolated from a pigtailed monkey (PT-STLV), which is 90% homologous to HTLV-I, was shown to be biologically active in transfection assay. In transfected cells, gp61 env , Pr55 gag , and the mature gag proteins p24, p21, and p15 were detected, and type C particles were produced. The virus could be transmitted from the transfectants to recipient cells by cocultivation. In this biologically active provirus clone, a coding frame, possibly for protease, was identified between the gag and pol genes. The corrected sequence of the protease region of HTLV-I was also found to have a single open reading frame overlapping the gag and pol genes, although it has an amber codon in the middle of the frame. Thus, a single coding frame, which is different from those of gag and pol, is common to proteases of the HTLV family including HTLV-I.

Social stimuli as incentives for delayed response performance by infant pigtailed macaques (Macaca nemestrina)

Six pigtailed macaque monkeys (Macaca nemestrina), ranging in age from 4.5 to 13.5 months, were studied longitudinally on a delayed response procedure in a spatial choice apparatus. In each trial the subjects were exposed to two stimulus animals, an unfamiliar adult female and a familiar age-mate. Prior work showed that such nursery-reared infants overwhelmingly prefer a familiar peer over an unfamiliar adult female. Therefore, the peer was considered to be a positive incentive and choosing the peer was defined as the “correct” response. After the infants were given visual exposure to the stimulus animals, an opaque door was lowered to block them from the subject's view. Then a single delay period of 0, 5, 15, 60, 120, 240, or 480 sec was introduced during 20-trial sessions. The delays were increased over sessions, with about two weeks between sessions. The subjects reliably chose the familiar peer after delays of up to 60 sec, with one subject maintaining correct choices even after 8-min delays. These results revealed that the delayed response performance of young macaques with social incentives was as good as, or better than, maximum performance levels reported for macaques with food incentives. Cues such as odors, sounds, and visual-postural orientation sets could not explain the performance levels at long delays found in this study.

Comparison of subjective lens preference to objective refractive error measurements in pigtail macaques.

Two measurements can be taken to determine the refractive error in human beings: a subjective, lens preference measurement and objective retinoscopy. This study determined the subjective refractive error in eight pigtailed monkeys by placing lenses of different powers in front of peepholes in a solid wall cage and recording the amount of time each subject used the holes. Retinoscopy measurements were then taken and compared to the subjective findings to determine the degree of similarity between these two refraction methods. The results showed a high correlation between the subjective measurements and the vertical ocular refraction (VOR) and spherical equivalent (SE) (rho = 0.96), further supporting generalizations made from nonhuman primate vision studies to human beings.

Immunopathology and histopathology of experimental chlamydial salpingitis.

Experimental infection of fallopian tubes was produced in four sexually mature pig-tailed monkeys (Macaca nemestrina) by intratubal inoculation with serovar E or F Chlamydia trachomatis. Infection was confirmed by reisolation of the organism from both the endosalpinx and the endocervix. An antibody response to the infecting strain of C. trachomatis was demonstrated in monkey sera and in cervical secretions by the microimmunofluorescence test. A cellular immune response to C. trachomatis was shown by the in vitro lymphocyte transformation assay. Histopathologic examination of the endosalpinx following infection showed epithelial degeneration and deciliation of ciliated cells. Lymphocytic infiltration into both submucosa and mucosa was present at day 7 and approximated areas of epithelial cell degeneration. Two control monkeys remained unresponsive throughout the study. These results indicate that the pig-tailed macaque should be a suitable model for further studies of the pathogenesis of, immune responses to, and therapy for acute C. trachomatis salpingitis.

Hb bali (Macaca) β80 (EF 4) Asn→Lys: The first hemoglobin variant found in the crab-eating monkey (Macaca fascicularis) on Bali Island, Indonesia

A variant hemoglobin due to structural change in the β chain was found in the central part of Bali island, Indonesia, during field studies on the genetic variation of the Indonesian crabeating monkey (Macaca fascicularis), and was named Hb Bali (Macaca). Structural analysis yielded the following results. (1) The amino acid sequence of the normal β chain of the crab-eating monkey coincided with that of the Japanese monkey (M. fuscata) and the pig-tailed monkey (M. nemestrina). (2) Asn at the 80th position from the amino terminal of the β chain was substituted by Lys in Hb Bali. This substitution appeared to have little harmful effect on the carrier, since the hematological characteristics of the heterozygous carriers were not different from those of normal individuals.

Sequence homoiogy of the simian retrovirus genome with human t-cell leukemia virus type I

A retrovirus highly related to human T-cell leukemia virus type I (HTLV-I) was isolated from a T-cell line established from a seropositive pig-tailed monkey and the provirus genome was molecularly cloned using HTLV-I as a probe. The monkey virus (STLV) had the genomic structure of the LTR- gag-pol-env-pX-LTR. Analysis of the env-pX-LTR region revealed the 90% homology of the nucleotide sequence with that of HT:V-I in each region. This high homology of the sequence indicates that STLV is a member of the HTLV family, but apparently different from HTLV-I. This suggests that the possibility of recent interspecies transmission from monkeys to humans in the endemic area is very small. From its similarity to HTLV, STLV should be useful as an animal model in studies on natural HTLV infection and leukemogenesis of HTLV in humans.

Wound healing after anterior and posterior subapical osteotomy

Changes in the process of wound healing and in the dental pulp were examined following anterior and posterior mandibular subapical osteotomies in pig-tailed macaque monkeys. Results of microangiographic and histologic investigations indicated that degenerative pulpal changes may occur following mobilization and repositioning of small dentoalveolar segments. The potential significance of such degenerative pulpal changes and the need for routine dental radiographic checkups following anterior and posterior mandibular dentoalveolar surgery are discussed.

Nimodipine improves outcome when given after complete cerebral ischemia in primates.

Twenty-seven pigtailed monkeys (Macaca nemestrina) were subjected to 17 min of complete cerebral ischemia followed by 96 h of intensive care treatment. Fourteen of the monkeys were assigned randomly to the treatment group and received nimodipine 10 micrograms . kg-1 5 min postischemia followed by 1 microgram . kg-1 . min-1 for 10 h. Six monkeys (three treated) failed to meet preestablished protocol criteria and were excluded. The remaining treated and untreated monkeys were well matched for age, sex, and other physiologic variables. Neurologic outcome at 96 h postischemia was significantly better in the nimodipine-treated monkeys than in the controls. Eight of the 11 treated animals had an apparent normal level of consciousness; four of these had no detectable neurologic deficits and a fifth had only a slight motor apraxia. Only two of the 10 untreated animals had an apparent normal level of consciousness, and all had major neurologic deficits. Histopathologic examination showed variable ischemic neuronal change and infarction to involve gray matter in distal arterial perfusion zones. Significant white matter changes were not observed. A histopathologic scoring system yielded a significantly better mean score for the treated group than for the untreated group, and there was significant correlation between neurologic function and histopathologic findings. The authors conclude that nimodipine improves the neurologic outcome when given after an episode of complete cerebral ischemia in primates, and they recommend controlled clinical trials in patients resuscitated after cardiac arrest.

Thiopental after Brain Ischemia in Monkeys. Cardiovascular and Electroencephalographic Effects

The cardiovascular and electroencephalographic (EEG) effects of thiopental were investigated, with and without preceding global brain ischemia (GBI). Four groups of pigtailed monkeys were used: Group I received thiopental 90 mg/kg over 1 h after 16 min GBI. Group II received thiopental 90 mg/kg over 1 h without preceding brain ischemia. Group III received 90 mg/kg over 1, 3, 6, or 8 h with varying infusion rates and no brain ischemia. Group IV, after 16 min GBI, received thiopental 90 mg/kg over 12 h with a gradually reduced infusion rate, keeping thiopental serum levels around 120-140 mumol X l-1 throughout the infusion. Large doses of thiopental (Group II) produced serious cardiovascular side-effects. With co-existing brain ischemia (Group I), these side-effects were much worse; five of six animals not receiving lidocaine prophylaxis suffered circulatory arrest. A prolongation of the Q-T interval on the electrocardiogram may be of pathogenetic importance. In contrast, lower thiopental blood levels, sufficient to depress the EEG to burst suppression or isoelectricity, were well tolerated with and without preceding brain ischemia (Groups IV and III).

Caudate electrochemical response following amphetamine administration in pigtail monkeys

In vivo electrochemical and heart rate (HR) recordings following amphetamine (AMPH) (0.8 mg/kg) and saline administration were made from caudate in four young adult pigtail ( M. nemestrina ) monkeys using linear sweep voltammetry. One hour following drug injection, two familiar humans served as test stimuli, and were visually exposed to the animals for 15-minute epochs each. One was threatening to the animals, and one was not. AMPH produced a significant increase in height of the electrochemical peak thought to represent oxidation of dopamine and its metabolites. Heart rate (HR) decreased during the time the peak height was increasing. HR and peak height increased during presentation of both humans under both AMPH and saline conditions. However, peak height increase under AMPH, but not saline, conditions discriminated the negative from neutral stimulus. The findings demonstrate that AMPH administration induces a significant increase in the height of a major electroactive peak in the caudate nucleus of pigtail monkeys, and further that such amphetamine-induced increases can be manipulated by altering the affective and/or emotional state of the animal.

Multifaceted therapy after global brain ischemia in monkeys.

The pathophysiology of postischemic encephalopathy is complex, and includes tissue acidosis, edema, hypoperfusion, membrane dysfunction, impaired energy production, and possibly hypermetabolism. We tested the hypothesis that this multifactorial clinical problem must be approached with multifaceted therapy, with specific treatment aimed at each of the above postischemic changes. Eighteen minutes of complete global brain ischemia was produced with a higher pressure neck cuff in pigtailed monkeys. Control treatment postischemia (n = 9): 1) Normotension (MAP greater than or equal to 80 mmHg) restored within 2 min postischemia, 2) controlled ventilation for 24 hours with PaCO2 = 25 mmHg, 3) normothermia, and 4) phenytoin seizure prophylaxis from 20 hours postischemia. Experimental treatment (n = 10): Control treatment plus the following modifications: 1) Hemodilution to hematocrit 25% at 1-4 min postischemia, 2) brief hypertension (MAP 130 mmHg for 5 min) after accomplished hemodilution, 3) hypothermia for 6 hours, 4) pentobarbital 30 mg/kg i.v., 5) dexamethasone 4 mg/kg i.v. Outcome was evaluated at 96 hours postischemia by overall performance categories (OPC) (OPC I = normal, OPC V = brain death), neurologic deficit (ND) scores (100% ND = brain death, 0% ND = normal), and histologic damage scores of the brains. Brain death developed in 1/9 control and 0/10 treated animals. The number of awake monkeys (OPC I and II) at 96 hours postischemia was significantly higher in the treated group (7/10) than in the control group (2/9) (p = 0.05). The median ND scores for the two groups were 16 and 35% respectively (p greater than 0.05). The results strongly suggest that postischemic treatment may be beneficial and that a multifaceted therapeutic approach is worth pursuing.