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PubMedDate not supplied

Serological and structural comparison of immunodeficiency viruses from man, African green monkey, rhesus monkey and sooty mangabey.

We have studied the serological relationship among the human immunodeficiency virus type 1 (HIV-1), and three simian immunodeficiency viruses (SIV). SIVagm was isolated from African green monkeys (Cercopithecus aethiops), and compared with the previously described isolates of SIVmac from a rhesus macaque (Macaca mulatta) and SIVsm from a sooty mangabey (Cercocebus atys). With respect to the glycoproteins, the simian viruses represent a subgroup apparently different from HIV. To classify HIV and SIV isolates further, we compared tryptic peptide maps of the core polypeptides p 18 and p 24 of HIV-2, three HIV-1 and five SIV isolates. Each peptide map was distinguishable, and differences are most prominent between the HIV-1 group and the SIVmac/SIVsm group. HIV-2 is very similar to SIVmac and SIVsm. The three SIVagm isolates form a more heterogeneous group. The p24s of all SIVagms are more similar to the p24s of HIV-1, but with respect to p 18, one isolate is similar to HIV-1, while the two others are more related to SIVmac, SIVsm, and HIV-2.

Cercopithecidae↗
PubMed1979

Effects of immunization with the beta-subunit of ovine luteinizing hormone on corpus luteum function in the rhesus monkey.

Rhesus monkeys immunized with the beta-subunit of ovine luteinizing hormone (oLHbeta) developed circulating antibodies which cross-reacted strongly with rhesus monkey chorionic gonadotropin. Normal ovulatory cycles continued, but the fertility of immunized monkeys as compared with that of controls was significantly reduced. Thus, the rhesus monkey represented a useful animal model for the study of certain aspects of an "antifertility vaccine." We investigated the effects of circulating antibodies to oLHbeta on corpus luteum function by measuring production rates (PRs) and peripheral concentrations of progesterone during the luteal phase of the menstrual cycle. Both parameters were significantly lower in immunized animals than in control animals. The length of the menstrual cycle was also significantly reduced. Progesterone PRs were also determined on days 10 and 15 after mating to test the assumption that the antifertility vaccine prevents pregnancy by interfering with "corpus luteum rescue" (the increase in PRs of progesterone usually occurring on day 15 after mating in fertilized animals). PRs increased from days 10 to 15 in pregnant controls, were unchanged in nonpregnant controls, and were significantly lower on day 15 in immunized monkeys as compared with nonpregnant and pregnant controls. These results suggest that "corpus luteum rescue" is suppressed in immunized animals.

Animals↗
PubMed1991

Insulin-like growth factors (IGFs) and IGF-binding proteins in the developing rhesus monkey.

Rhesus monkeys follow a developmental pattern of serum insulin-like growth factor-I (IGF-I) levels similar to that found in humans. In these monkeys, serum IGF-I levels peak during puberty (2.5-4.5 yr of age in males). We have examined the developmental pattern of IGF-binding protein-1 (IGFBP-1), -2, and -3 in serum by Western ligand blotting, the levels of IGFBP-3, IGF-I, and IGF-II in serum by RIA, and the IGFBP mRNA levels of IGFBP-1, -2, and -3 in the livers of rhesus monkeys from fetal life through adulthood by Northern analysis. The pattern of the serum levels of the IGFBPs reflected the liver mRNA levels of the IGFBPs. The IGFBP-1 and IGFBP-2 liver mRNA and serum levels were highest in the fetus and first year of life and were very low after 4 yr of age. Conversely, the IGFBP-3 liver mRNA and serum levels were relatively low early in life and peaked during puberty. The serum levels of IGF-I and IGF-II were strongly correlated with the level of IGFBP-3. We conclude that the developmental pattern of IGFBPs in the rhesus monkey is similar to that in the human, and that serum IGFBP levels are probably regulated by the rate of IGFBP mRNA synthesis.

Aging↗
PubMed1979

Induction of congenital hydrocephalus with mumps virus in rhesus monkeys.

Rhesus monkey fetuses were inoculated intracerebrally with wild-type mumps virus near the beginning of the last third of the gestation period. Within three days after inoculation, mumps virus was isolated from many fetal tissues. Thirteen animals receiving virus were delivered at term. Five of these showed slight to severe hydrocephalus. Hydrocephalus was most prominent in the posterior horns of the lateral ventricles, but other lesions occurred at various levels of the ventricular system. Virus was isolated from three animals at one day of age (two months after inoculation). However, mumps virus was not recovered from one-month-old monkeys. The recovery of mumps virus from newborn rhesus monkeys two months after inoculation suggests that attempts should be made to document similar persistence of the virus in humans. Furthermore, this model indicates that mumps virus infection in humans may result in hydrocephalus.

Amniotic Fluid↗
PubMed1992

Evaluation of the discriminative stimulus and reinforcing effects of sertraline in rhesus monkeys.

Rhesus monkeys (N = 4) were allowed to self-administer cocaine (0.03 mg/kg/injection) under a fixed-ratio 10 (FR 10) schedule during daily 2-h experimental sessions. When responding was stable, a variety of doses of sertraline, a serotonin reuptake blocker under development as an antidepressant, were made available for self-administration. Baseline conditions were reinstated between doses of sertraline. Cocaine 0.03 mg/kg/injection maintained high rates of injection, while total saline injections decreased to low levels within four to seven sessions. Sertraline (0.05-0.4 mg/kg/injection) did not maintain self-administration above saline levels in three of the four monkeys. In the fourth, responding was marginally above saline levels at two doses but was not systematically related to dose. In a second experiment, rhesus monkeys (N = 6) were trained to discriminate either d-amphetamine (0.56-1.0 mg/kg, IG) or pentobarbital (10 mg/kg, IG) from saline in a discrete-trials shock avoidance/escape paradigm. Sertraline (4.0-32 mg/kg) failed to substitute for either d-amphetamine or pentobarbital as a discriminative stimulus. These results suggest that sertraline is unlikely to have abuse potential in humans and is unlikely to have either d-amphetamine-like or pentobarbital-like subjective effects.

1-Naphthylamine↗
PubMed1987

Disseminated cytomegalovirus infection in immunodeficient rhesus monkeys.

Rhesus monkeys experimentally infected with the lentivirus SIV/Delta become immunodeficient and often die of opportunistic infections. The most frequent of these is cytomegalovirus (CMV). The lesions due to reactivated CMV infection in 14 SIV-infected monkeys were reviewed. Changes due to CMV were observed in the brain, lung, lymph node, liver, spleen, small intestine, testicle, nerves, and arteries. Disseminated CMV infection in immunodeficient rhesus monkeys is a useful model for studying the pathogenesis, treatment, and prevention of similar infections in immunodeficient human beings.

Animals↗
PubMed1975

Negative reinforcing properties of some psychotropic drugs in drug-naive rhesus monkeys.

Rhesus monkeys, previously trained to avoid electric shock, pressed a lever to extinguish a light associated with an intravenous drug infusion scheduled to occur 30 seconds after the onset of the light. Each response when the light was on terminated the light for a 1-minute time-out period (avoidance); a response during the infusion terminated the infusion (escape). Under these conditions the monkeys tolerated a high number of saline infusions. Saline was replaced by different doses of chlorpromazine, lysergic acid diethylamide (LSD) and pentobarbital each for six successive daily 2-hour sessions. Infusions of chlorpromazine (5.0-20 mug/kg/infusion) or LSD (1.0-2.5 mug/kg/infusion) generated and maintained avoidance/escape behavior, whereas most of the infusions of pentobarbital (10-100 mu/kg/infusion) were tolerated. In rhesus monkeys with no previous drug experience, chlorpromazine and LSD, but not pentobartital, have negative reinforcing properties.

Animals↗
PubMed1990

Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys.

Rhesus monkeys given pre- and postnatal diets deficient in n-3 essential fatty acids develop low levels of docosahexaenoic acid (22:6 n-3, DHA) in the cerebral cortex and retina and impaired visual function. This highly polyunsaturated fatty acid is an important component of retinal photoreceptors and brain synaptic membranes. To study the turnover of polyunsaturated fatty acids in the brain and the reversibility of n-3 fatty acid deficiency, we fed five deficient juvenile rhesus monkeys a fish oil diet rich in DHA and other n-3 fatty acids for up to 129 weeks. The results of serial biopsy samples of the cerebral cortex indicated that the changes of brain fatty acid composition began as early as 1 week after fish oil feeding and stabilized at 12 weeks. The DHA content of the phosphatidylethanolamine of the frontal cortex increased progressively from 3.9 +/- 1.2 to 28.4 +/- 1.7 percent of total fatty acids. The n-6 fatty acid, 22:5, abnormally high in the cerebral cortex of n-3 deficient monkeys, decreased reciprocally from 16.2 +/- 3.1 to 1.6 +/- 0.4%. The half-life (t 1/2) of DHA in brain phosphatidylethanolamine was estimated to be 21 days. The fatty acids of other phospholipids in the brain (phosphatidylcholine, -serine, and -inositol) showed similar changes. The DHA content of plasma and erythrocyte phospholipids also increased greatly, with estimated half-lives of 29 and 21 days, respectively. We conclude that monkey cerebral cortex with an abnormal fatty acid composition produced by dietary n-3 fatty acid deficiency has a remarkable capacity to change its fatty acid content after dietary fish oil, both to increase 22:6 n-3 and to decrease 22:5 n-6 fatty acids. The biochemical evidence of n-3 fatty acid deficiency was completely corrected. These data imply a greater lability of the fatty acids of the phospholipids of the cerebral cortex than has been hitherto appreciated.

Animals↗
PubMed1977

Methyl alcohol poisoning. II. Development of a model for ocular toxicity in methyl alcohol poisoning using the rhesus monkey.

Rhesus monkeys were intoxicated with methyl alcohol, using an initial dose of 2 gm/kg and subsequent doses were administered in order to maintain an attenuated and prolonged state of intoxication. Arterial blood samples were drawn for methyl alcohol, formate, PO2, PCO2, and pH, which were monitored periodically throughout the course of the experiment. With the use of these procedures monkeys developed metabolic acidosis with the accumulation of formic acid in the blood and a corresponding decrease in blood bicarbonate. These animals served as models, which allowed for ocular evaluation for early signs related to methyl alcohol poisoning. A mechanism to explain toxicity is proposed and discussed.

Acidosis↗
PubMed1977

Endocrine regulation of fetal development and its relation to parturition in the rhesus monkey.

Rhesus monkey fetuses were surgically prosencephalectomized (Type 2) or functionally hypophysectomized (Type 1) at 75 days gestation, then returned to the uterus until elective Caesarean section on day 145--150 (term 167 days). Deprivation of fetal hypothalamic releasing factors in Type 2 and fetal pituitary tropic hormones in Type 1 significantly delayed the ontogeny and functional development of fetal endocrine tissues. Bone ossification and growth were significantly retarded in Type 1 only, not in Type 2. In Type 1 the body and all organs except the endocrine glands were about half normal weight. The adrenals, thyroids, ovaries and testes were histologically abnormal and about one-tenth normal weight. Non-endocrine organs were histologically similar to 110-130-day fetuses. Thyroxine (T4) concentrations were significantly depressed in Type 1 fetal and maternal plasma at Caesarean section but normal in Type 2. Cortisol concentrations were normal in Type 1 fetal and maternal plasma. Types 1 and 2 plasma oestradiol concentrations were significantly lower in mothers but normal in fetuses. Type 1 placentas produced significantly less progesterone in vitro than normal. Fetal endocrine autonomy is indicated (thyrotropin-releasing factor excepted). Many of the hypothalamic and anterior pituitary hormones do not pass in effective amounts from mother to fetus. Fetal endocrine autonomy is a prerequisite for the control of both development and parturition.

Adrenal Glands↗
PubMed1975

Hepatic and metabolic effects of ethanol on rhesus monkeys.

Rhesus monkeys were tube-fed 100 calories per kg of a liquid diet based on casein in which 41% of the calories were derived from grain alcohol. The alcohol intake was 5.8 g per kg per day. Control diets contained isocaloric amounts of glucose. The protein content of the diet was 15% and fat supplied 21% of the calories. After 28 days the animals which had been fed ethanol developed hepatic fatty change and serum L.D.H. levels were elevated. The most striking electron microscopic changes in the alcohol animals were mitochondrial swelling, focal cytoplasmic degradation, and dilatation of the rough endoplasmic reticulum. In the monkeys which had received ethanol the metabolism of alcohol increased from 17.4 mg per 100 ml per hour to 26.6 mg and antipyrene half-life decreased from 61.0 minutes to 49.9 minutes. The carbohydrate animals showed no significant change in alcohol metabolism or antipyrene half life. The ethanol animals lost weight significantly while the carbohydrate animals gained significantly. The metabolic effects of alcohol thus were not reproduced by glucose. Administration of phenobarbital at 30 mg per kg for 5 days increased alcohol metabolism from 16.5 mg per hour to 22.5 mg per hour and shortened antipyrene half life from 76.5 minutes to 33.6 minutes. Alcohol and phenobarbital both induced enhanced drug metabolism but alcohol was a more powerful inducer of its own metabolism than phenobarbital. Phenobarbital on the other hand was a better inducer of antipyrene metabolism than alcohol.

Animals↗
PubMed1986

Effects of clonidine and morphine on opioid withdrawal in rhesus monkeys.

Rhesus monkeys undergoing opioid withdrawal either due to withholding morphine administration for 14 h or due to administration of naloxone, were treated with or due to administration of naloxone, were treated with either morphine or clonidine. Morphine eliminated all of the withdrawal signs that developed when morphine was withheld for 14 h. Clonidine also eliminated some but not all signs that developed when morphine was withheld. The frequencies of individual signs prior to drug administration were directly related to the minimal doses necessary to eliminate signs for morphine but not for clonidine. Morphine also eliminated most of the signs precipitated by naloxone, whereas clonidine did not eliminate as many of the naloxone-precipitated signs. Additionally, some of the naloxone-precipitated signs that were eliminated by clonidine were not eliminated by morphine. The present results are consistent with clinical findings indicating an efficacy of clonidine in the treatment of opioid withdrawal through a non-opioid mechanism.

Animals↗
PubMed1979

Elevation of blood lead concentration by confinement in the rhesus monkey.

Rhesus monkeys were exposed to lead (Pb) acetate under various regimens during the first 12 months of life. At 30 months of age, these animals and unexposed controls were confined to an unfamiliar experimental chamber for one week. Serum cortisol concentration and Pb concentration in whole blood (PbB) were measured prior to, during, and after this confinement. Cortisol concentrations rose 60--90% within 2 hours of confinement, and declined to baseline levels after 98 hours of confinement. Mean baseline PbB levels reflected the state of clearance of the previously-ingested lead, rose 25--35% within 2 hours of confinement, and reached mean maximum levels as much as 100% above baseline after 98 hours of confinement. The data are discussed in terms of hormonal mobilization of Pb stored in bone, and subgest (1) that this storage is multicompartmental, (2) that more than one process is probably involved in its mobilization, (3) that cortisol probably does not directly affect PbB levels, and (4) that stress should be considered a potential factor in determining the PbB in studies of Pb metabolism.

Animals↗
PubMed1992

Effects of increasing response requirement on choice between cocaine and food in rhesus monkeys.

Rhesus monkeys were trained in a discrete-trials choice procedure and allowed to choose between intravenous injections of cocaine (0.01-1.0 mg/kg/injection) and food presentation (1 or 4 pellets; 1 g/pellet) during daily 7-h experimental sessions. When each reinforcer was available under a fixed-ratio (FR) 30 schedule, the frequency of cocaine choice and the total drug intake increased in a dose-related manner for all monkeys. When the FR for cocaine was differentially increased, the frequency of cocaine choice decreased, shifting the cocaine dose-response function to the right and/or downward. When the FR for cocaine was at least 480, cocaine preference could not be recovered up to doses of 1.0 mg/kg/injection. In a second experiment, when the response requirement for food was differentially increased, the frequency of cocaine choice increased. These results demonstrate that altering the response requirement for cocaine or for alternative reinforcers that are available can substantially affect cocaine self-administration.

Animals↗
PubMed1978

Localization and detection of visual stimuli following superior colliculus lesions in rhesus monkeys.

Rhesus monkeys were trained to fixate a central stimulus and to detect and localize a 50 msec light flash presented 6-80 degrees on either side of the central stimulus. Following large lesions of the superior colliculus, they showed persistent deficits in localizing flashes presented 43-80 degrees from the fixation stimulus. However, they were not consistently impaired when the flashes were presented more centrally, and their performance with peripheral stimuli improved when the stimulus duration was 1 sec. Thus, the superior colliculus appears to be necessary for the localization of brief visual stimuli in the far periphery.

Animals↗
PubMed1978

Dorsolateral prefrontal cortex lesions and discrimination of movement-produced cues by rhesus monkeys.

Rhesus monkeys were trained on a conditional discrimination in which sequences of either 32 or 64 lever presses served as discriminative stimuli. For half the subjects, reinforcement was contingent upon choice of a red response key following a sequence of 32 presses (FR 32), and a white key after FR 64, with the position of the two key colors randomized across trials. The remaining subjects were reinforced for left key presses after FR 64, and right key presses after FR 32, with key color again randomized across trials. Ablation of dorsolateral prefrontal cortex resulted in postoperative deficits in all subjects, although 6 of 8 eventually remastered the task. This recovery was investigated in a second experiment, in which psychophysical functions were generated by varying the length of the shorter FR. Although dorsolateral lesions again produced a severe disruption in performance, the post-operative functions eventually obtained were identical to the preoperative functions. This pattern of marked impairment in retention of fixed ratio discriminations, but no change in asymptotic capacity, suggests participation of dorsolateral prefrontal cortex in processing kinesthetic information, possibly analogous to the role of inferior temporal cortex in processing visual information.

Animals↗
PubMed1989

Intermittent naloxone attenuates the development of physical dependence on methadone in rhesus monkeys.

Rhesus monkeys that received 15 daily injections of methadone (2 mg/kg i.m.) exhibited a characteristic opiate withdrawal syndrome after injection of naloxone (0.5 mg/kg i.m.) on the 16th day. In comparison, injection of naloxone (0.5 mg/kg i.m.) once every 2 days during a similar 15 day methadone treatment period in these same monkeys significantly attenuated the severity of the opiate withdrawal syndrome exhibited after naloxone injection on the 16th day. Each naloxone administration during the 15 day methadone treatment period elicited an opiate withdrawal syndrome that did not significantly differ on each of the 7 days it was given and was less severe than the syndrome precipitated by naloxone following 15 days of methadone without intermittent naloxone. The lack of increments in the withdrawal response to the seven naloxone injections during the 15 days of methadone treatment and the attenuation of the withdrawal response to naloxone on day 16 after intermittent naloxone administration during the 15 day methadone treatment period support the hypothesis that naloxone modifies opiate receptor mechanisms so that they revert to an agonist-naive state following antagonist exposure. These findings suggest that various agonist and antagonist opiate drug combinations or mixed agonist-antagonist drug could be clinically useful in the management of situations where physical dependence on opiates is a problem.

Animals↗