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PubMed1974

Two unlike patterns of random-ratio responding associated with different eating habits in rhesus monkeys.

Four rhesus monkeys were exposed to an identical series of schedules that specified a uniform probability of reinforcement for every response. As probability was lowered slowly in 10 steps of 20 sessions each from 1.0 through 0.01, two distinct patterns of responding emerged. Two subjects showed high, pause-free response rates that increased with each successive reduction in reinforcement probability. The other two showed consistent post-reinforcement pausing at all probabilities, including 1.0, and substantially lower response rates that peaked at the moderate probability values of 0.04 and 0.03. This low-rate pattern was found to be correlated with a pre-experimental preference in the two subjects for mouthing and chewing food pellets one at a time, while the former high-rate, pause-free pattern was linked to a long-standing habit of "pouch feeding" in the other monkeys. These idiosyncratic collateral behaviors that differentiated the schedule performances appeared neither superstitious in origin, nor useful in the case of the low-rate monkeys.

Journal Article↗
PubMed1999

Discriminative stimulus effects of the nonpeptidic delta-opioid agonist SNC80 in rhesus monkeys.

Five rhesus monkeys were trained to discriminate the nonpeptidic, delta-opioid agonist SNC80 (0.32 mg/kg i.m.) from saline by using a food-reinforced drug-discrimination procedure. Cumulative doses of SNC80 produced a dose-dependent increase in SNC80-appropriate responding and a dose-dependent decrease in response rate. In time-course studies, peak effects of the training dose of SNC80 were observed after 15 min, and these effects diminished over 240 min. In substitution studies, other piperazinyl benzamide delta agonists (SNC86, SNC162, and SNC243A) substituted for SNC80 with relative potencies similar those of SNC80. However, SNC67, the (-)-enantiomer of SNC80, did not occasion SNC80-appropriate responding up to a dose (32.0 mg/kg) that produced convulsions in one monkey. The mu agonists morphine and fentanyl and the kappa agonists U-50,488 and enadoline failed to substitute for SNC80 up to doses that eliminated responding. Two nonopioids (the N-methyl-D-aspartate antagonist ketamine and the monoamine reuptake inhibitor cocaine) also produced primarily saline-appropriate responding. Both the discriminative stimulus and rate-decreasing effects of SNC80 were antagonized by the delta-selective antagonist naltrindole (0.01-1.0 mg/kg) but not by doses of the opioid antagonist quadazocine (0.1-1.0 mg/kg) that block the effects of mu and kappa agonists. These data suggest that the discriminative stimulus effects of SNC80 are mediated by delta-opioid receptors and that the discriminative stimulus effects of delta opioids in primates can be differentiated from the effects of other opioid and nonopioid compounds.

Analgesics, Opioid↗
PubMed1992

[Effects of dexamethasone and cyclophosphamide on development of exo-erythrocytic form of Plasmodium cynomolgi bastianellii in rhesus monkey].

The rhesus monkeys (Macaca mulatta) challenged with Plasmodium cynomolgi bastianellii sporozoites were treated with im dexamethasone (Dex) 1 mg.kg-1.d-1 x 7 d and cyclophosphamide (Cyc) 25 mg.kg-1.d-1 x 3d, respectively. On d 7 after challenge, serial sections of liver biopsy stained with HE revealed that the distributive density and size of exo-erythrocytic (EE) form of the parasites showed no difference between medicated and control monkeys. The prepatent period of the primary attack and the relapse patterns after the treatment of Dex and Cyc were also similar to each other. The radically cured monkeys challenged with the Plasmodium erythrocytic form were reinfected with sporozoites, the relapses were much less than those in control monkeys, but the density and size of EE form in liver were similar to those in control monkeys. These results suggest that Dex and Cyc exert no effect on the development of EE form (including hypnozoite) in the monkeys.

Animals↗
PubMed1988

Induction of antigen-specific bronchial reactivity to trimellityl-human serum albumin by passive transfer of serum from humans to rhesus monkeys.

A rhesus monkey model was developed to demonstrate the pathogenetic role of IgE to chemical hapten-protein conjugates in causing human occupational asthma from reactive chemicals. Serum from a worker with trimellitic anhydride (TMA) asthma that contained high titers of IgE, IgG, IgM, and IgA to trimellityl-human serum albumin (TM-HSA) was aerosolized into the lungs of two monkeys to afford passive airway sensitization. After the monkeys were challenged with aerosolized TM-HSA, pulmonary functions demonstrated acute airway responses similar to that of Ascaris antigen-induced, IgE-mediated bronchospasm in Ascaris-sensitive monkeys. The monkeys had no airway reactivity when challenged with TM-HSA 1 week after the first positive TM-HSA response elicited with passive sensitization. Passive cutaneous reactivity to TM-HSA was also elicited by the donor serum, but heat-treated donor serum failed to confer cutaneous or bronchial reactivity. These results indicate that airway reactivity in this passive-transfer monkey model of TMA asthma is an antigen-specific response mediated by heat-labile serum factors, presumably IgE to TM-HSA, and does not occur by irritant mechanisms. This experimental model could become a valuable system for evaluating the role of IgE to hapten-protein conjugates in the immunopathogenesis of asthma caused by other reactive chemicals capable of acting as haptens. We postulate that immunologic and clinical features should be consistent with asthma caused by such reactive chemicals and mediated by such mechanisms.

Animals↗
PubMed1987

Pharmacological analysis of the apomorphine discriminative stimulus in rhesus monkeys.

Four rhesus monkeys were trained to discriminate apomorphine (APO) from saline in a two lever, food-reinforced drug discrimination paradigm. After acquisition of the discrimination (average = 161 sessions), they were tested with a series of compounds selected to characterize the neuronal mechanism(s) of the discrimination and to determine whether the site of action was central or peripheral. APO produced a dose-related increase in the percentage of responses that occurred on the drug lever during test sessions. The D2 dopamine (DA) agonist piribedil substituted completely for APO and the D2 DA antagonist pimozide antagonized the APO discriminative stimulus in a manner consistent with a competitive antagonism. On the other hand, the D1 agonist SKF 38393 engendered principally saline lever responding in all monkeys, whereas the D1 DA antagonist SCH 23390 was ineffective as an APO antagonist. The APO effect was neither mimicked by DA nor blocked by the D2DA antagonist domperidone, both of which fail to cross the blood-brain barrier to any significant extent. In substitution tests the norepinephrine reuptake blocker nisoxetine, the serotonin agonist quipazine and the cholinesterase inhibitor physostigmine, as well as d-amphetamine, cocaine and morphine engendered principally saline lever responding up to doses that substantially reduced rate of responding. Taken together these results suggest that the APO discriminative stimulus is based principally upon an action at a D2 receptor in the central nervous system and that this preparation can be used for studying the functional properties of central nervous system D2 receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

A quantitative assessment of phencyclidine dependence produced by oral self-administration in rhesus monkeys.

Three rhesus monkeys were trained to self-administer orally delivered phencyclidine (PCP) and water under concurrent fixed-ratio schedules. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. PCP deliveries exceeded water deliveries throughout the experiment, indicating that the drug was functioning as a positive reinforcer. The monkeys were also trained to lever press under a fixed-ratio 64 or fixed-ratio 80 schedule of food delivery. Food was available during three 1 hr periods each day, with 6.5 hr of liquid availability between each food component. After behavior stabilized for at least 10 days under these conditions, water was substituted for PCP for 2, 4, 8 or 24 days. Food-maintained responding was severely disrupted for the first 2 days of water substitution, with a steady recovery over the following 6 days. The monkeys were noticeably irritable during water substitution, but there were no other physical signs of PCP withdrawal. Disruptions in food-maintained responding were immediately reversed when PCP was reinstated. Subsequently, the PCP concentration was varied (0.062, 0.125, 0.25, 0.5 and 1 mg/ml), and PCP intake (milligrams per kilogram), as well as the magnitude of disruptions in pellet deliveries (upon termination of PCP access), also varied directly with PCP intake. The amount of PCP intake was also altered by limiting PCP (0.25 mg/ml) access to every 2nd or 4th day, with water available on intervening days. Pellet deliveries were substantially disrupted during water substitution, and food-maintained responding immediately returned to control levels when PCP became available.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1987

Renal medullary solute depletion resulting from psychogenic polydipsia in a rhesus monkey.

A rhesus monkey developed psychogenic polydipsia after a change in feeding regimen was instituted. Hyposthenuria, hyponatremia, hypochloremia, and an abnormal calculated plasma osmolality were found. Water deprivation testing and administration of antidiuretic hormone indicated that renal medullary solute depletion had resulted from the prolonged polyuria. Restricted water consumption resulted in resolution of the electrolyte abnormalities and restored ability to excrete concentrated urine.

Animals↗
PubMed1978

The reinforcing properties of procaine and d-amphetamine compared in rhesus monkeys.

Twelve rhesus monkeys were studied under a fixed-ratio (FR) schedule of intravenous procaine or d-amphetamine injection from 8 A.M. to 4 P.M. daily. Under the FR schedule, every nth lever press produced an injection. The FR value (n) and the dose per injection of procaine and d-amphetamine were varied systematically. At a FR value of 10, responding was maintained by doses of procaine ranging from 0.125 to 12 mg/kg/injection and by doses of d-amphetamine ranging from 0.01 to 0.1 mg/kg/injection. At doses of 1 mg/kg/injection of procaine and 0.1 mg/kg/injection of d-amphetamine, responding was maintained at FR values up to 100 by procaine and d-amphetamine but not by saline. Responding and drug intake were relatively constant throughout each 8-hour session with procaine, but responding tended to decrease and was more variable over the session with d-amphetamine. No toxic effects were observed in doses up to 6 mg/kg/injection with procaine. At this dose, eating and drinking ceased during the period of access to the drug. One of the four monkeys died at 8 mg/kg/injection of procaine. At 12 mg/kg/injection all three monkeys tested showed signs of toxicity.

Animals↗
PubMed1982

Early colonic lesions in experimental Shigella infection in rhesus monkeys: revisited.

Rhesus monkeys (Macaca mulatta), given 3 x 10(8) to 5 x 10(10) Shigella flexneri 2a orally, developed signs of acute shigellosis within 24 hours. A diffuse acute colitis was well established at 48 hours. The inflammatory reaction was confined to the mucosa. The submucosa showed only edema. The shigellae were found predominantly in the columnar cells of the surface epithelium, less frequently in those of the crypt, and least frequently in the lamina propria. Shigella bacilli invaded the columnar cells from the intestinal lumen. The bacilli multiplied within epithelial cells and spread laterally to adjacent epithelial cells and penetrated the lamina propria. The bacterial invasion affected epithelial cells unevenly and resulted in the disappearance of goblet cells and pyknotic shrinkage of the surface epithelial cells. Epithelial cells had abnormal and accelerated exfoliation which resulted in multifocal epithelial defects. There was a distinct correlation between the quantity of bacilli present in tissues and the intensity of the inflammatory response. The small intestines were spared.

Animals↗
PubMed1984

Salt hunger in the rhesus monkey.

Five rhesus monkeys (Macaca mulatta) were placed on a low-sodium diet and given injections of furosemide in order to promote sodium loss. The results indicated that these methods elicit a substantial and specific salt hunger. Issues surrounding salt hunger are discussed.

Animals↗
PubMed1982

Early colonic lesions in experimental Shigella infection in rhesus monkeys: revisited.

Rhesus monkeys (Macaca mulatta), given 3 X 10(8) to 5 X 10(10) Shigella flexneri 2a orally, developed signs of acute shigellosis within 24 hours. A diffuse acute colitis was well established at 48 hours. The inflammatory reaction was confined to the mucosa. The submucosa showed only edema. The shigellae were found predominantly in the columnar cells of the surface epithelium, less frequently in those of the crypt, and least frequently in the lamina propria. Shigella bacilli invaded the columnar cells from the intestinal lumen. The bacilli multiplied within epithelial cells and spread laterally to adjacent epithelial cells and penetrated the lamina propria. The bacterial invasion affected epithelial cells unevenly and resulted in the disappearance of goblet cells and pyknotic shrinkage of the surface epithelial cells. Epithelial cells had abnormal and accelerated exfoliation which resulted in multifocal epithelial defects. There was a distinct correlation between the quantity of bacilli present in tissues and the intensity of the inflammatory response. The small intestines were spared.

Animals↗
PubMed1975

Transmission of hepatitis B to the rhesus monkey.

The rhesus monkey does provide a suitable laboratory animal model for studying hepatitis B virus and for investigating various aspects of interaction between this infectious agent and the host. This species of non-human primate, however, offers a less sensitive animal model for hepatitis B infection than the chimpanzee.

Animals↗
PubMed1976

Behavior maintained under a second-order schedule by intramuscular injection of morphine or cocaine in rhesus monkeys.

Three rhesus monkeys lived in primate cages provided with response keys and enclosed in isolation chambers. During experimental sessions on Monday, Wednesday and Friday, the chamber door was closed and every 10th key-pressing response during a 60-minute interval produced a 2-second red light, but had no other programmed consequences (the 10-response fixed-ratio component of the second-order schedule; FR 10). The first FR 10 component completed after the 60-minute interval had elapsed produced a red light which remained on for 2 minutes while the chamber door was opened; the monkey then extended his arm and was given an intramuscular injection of drug (the 60-minute fixed-interval component of the second-order schedule; FI 60 min). Under this second-order schedule of intramuscular drug injection, repeated sequences of rapid responding were maintained during each session by 0.75 to 3.0 mg/kg injections of either morphine or cocaine. Patterns of responding characteristic of FR schedules were controlled by the 2-second red lights; a pause in responding after each 2-second red light was followed by a sustained high rate of responding until the light was produced again. Pauses in responding became progressively shorter as time elapsed in the 60-minute interval. When saline injections were substituted for drug injections, responding markedly decreased. When responding was maintained by 3.0 mg/kg morphine injections, pretreatment with 0.03 mg/kg of nalorphine increased responding, while pretreatment with 0.1 or 0.3 mg/kg of nalorphine decreased responding.

Animals↗
PubMed1976

Intracerebral oxygen and carbon dioxide tensions in the rhesus monkey.

Five rhesus monkeys (M. mulatta) were prepared by surgical placement of a stainless steel implant in the parietal area of the skull. The implant was designed to firmly hold a Teflon coated membrane of a medical mass spectrometer in an intracerebral position. Animals were consecutively exposed to varying ambient oxygen concentrations from 11% to 21%. Intracerebral PO2 and PCO2 and arterial PO2 were all stimultaneously recorded for computer analysis. Results indicate an almost linear relationship between cerebral PO2 and ambient PO2 as well as between cerebral PO2 and arterial PO2. With an ambient oxygen concentration of 21%, the cerebral Po2 and Pco2 were 13.5 +/- 3.5 mm Hg and 50.4 +/- 7.9 mm Hg, respectively. With an ambient oxygen concentration of 10.7%, these values decreased to 2.5 +/- 2.7 mm Hg and 38.0 +/- 5.6 mm Hg.

Animals↗
PubMed1978

Some Golgi data on visual cortex of the rhesus monkey.

The rhesus monkey's visual cortex was studied on Golgi material. The terminal arborization of the geniculate fibres and non-specific vertical fibres have been analysed. The interneurons (intrinsic neurons) of the area described in detail and classified on the basis of their axonal and dendrite arborizations. The stellate neurons in layer IV are discussed.

Animals↗
PubMed2005

Deoxycytidyl-deoxyguanosine oligonucleotide classes A, B, and C induce distinct cytokine gene expression patterns in rhesus monkey peripheral blood mononuclear cells and distinct alpha interferon responses in TLR9-expressing rhesus monkey plasmacytoid dendritic cells.

To determine if deoxycytidyl-deoxyguanosine oligonucleotides (CpG ODN) can be used effectively as nonspecific inducers of innate immune defenses for preventative or therapeutic interventions in infectious disease models for nonhuman primates, the present study evaluated the response of rhesus monkey peripheral blood mononuclear cells to three different synthetic CpG ODN classes by defining the cytokine gene expression patterns and by characterizing IFN-alpha/beta responses. Depending on the type and dose of CpG ODN used for stimulation, distinct gene expression patterns were induced. CpG ODN class A (CpG-A ODN) and CpG-C ODN, but not CpG-B ODN, were potent inducers of alpha interferon (IFN-alpha), and this response was due to IFN-alpha production by TLR9-positive plasmacytoid dendritic cells. Importantly, there was a dose-dependent increase in IFN-alpha responses to CpG-A ODN but a dose-dependent decrease in IFN-alpha responses by CpG-B ODN. The most sustained IFN-alpha response was induced by CpG-A ODN and was associated with a stronger induction of interferon regulatory factor 7 and the induction of several interferon-stimulated genes. In contrast, and independent of the dose, CpG-B ODN were the weakest inducers of IFN-alpha but the most potent inducers of proinflammatory cytokines. CpG-C ODN induced cytokine gene expression patterns that were intermediate between those of CpG-A and CpG-B ODN. Thus, the different types of CpG ODN induce different post-TLR9 signaling pathways that result in distinct cytokine gene expression patterns. Based on these findings, A and C class CpG ODN, but not B class CpG ODN, may be particularly suited for use as therapeutic or prophylactic antiviral interventions.

Animals↗
PubMed2000

The primary sequence of rhesus monkey rhadinovirus isolate 26-95: sequence similarities to Kaposi's sarcoma-associated herpesvirus and rhesus monkey rhadinovirus isolate 17577.

The primary sequence of the long unique region L-DNA (L for low GC) of rhesus monkey rhadinovirus (RRV) isolate 26-95 was determined. The L-DNA consists of 130,733 bp that contain 84 open reading frames (ORFs). The overall organization of the RRV26-95 genome was found to be very similar to that of human Kaposi sarcoma-associated herpesvirus (KSHV). BLAST search analysis revealed that in almost all cases RRV26-95 coding sequences have a greater degree of similarity to corresponding KSHV sequences than to other herpesviruses. All of the ORFs present in KSHV have at least one homologue in RRV26-95 except K3 and K5 (bovine herpesvirus-4 immediate-early protein homologues), K7 (nut-1), and K12 (Kaposin). RRV26-95 contains one MIP-1 and eight interferon regulatory factor (vIRF) homologues compared to three MIP-1 and four vIRF homologues in KSHV. All homologues are correspondingly located in KSHV and RRV with the exception of dihydrofolate reductase (DHFR). DHFR is correspondingly located near the left end of the genome in RRV26-95 and herpesvirus saimiri (HVS), but in KSHV the DHFR gene is displaced 16,069 nucleotides in a rightward direction in the genome. DHFR is also unusual in that the RRV26-95 DHFR more closely resembles HVS DHFR (74% similarity) than KSHV DHFR (55% similarity). Of the 84 ORFs in RRV26-95, 83 contain sequences similar to the recently determined sequences of the independent RRV isolate 17577. RRV26-95 and RRV17577 sequences differ in that ORF 67.5 sequences contained in RRV26-95 were not found in RRV17577. In addition, ORF 4 is significantly shorter in RRV26-95 than was reported for RRV17577 (395 versus 645 amino acids). Only four of the corresponding ORFs between RRV26-95 and RRV17577 exhibited less than 95% sequence identity: glycoproteins H and L, uracil DNA glucosidase, and a tegument protein (ORF 67). Both RRV26-95 and RRV17577 have unique ORFs between positions 21444 to 21752 and 110910 to 114899 in a rightward direction and from positions 116524 to 111082 in a leftward direction that are not found in KSHV. Our analysis indicates that RRV26-95 and RRV17577 are clearly independent isolates of the same virus species and that both are closely related in structural organization and overall sequence to KSHV. The availability of detailed sequence information, the ability to grow RRV lytically in cell culture, and the ability to infect monkeys experimentally with RRV will facilitate the construction of mutant strains of virus for evaluating the contribution of individual genes to biological properties.

Amino Acid Sequence↗
PubMed1978

Endocrine effects of chlorinated hydrocarbons in rhesus monkeys.

After the rhesus monkey was demonstrated to be a suitable model for man in both metabolic and endocrinological studies, effects of hexachlorobenzene (HCB) and polychlorinated biphenyls (PCB) on the pattern of sexual hormones in cycling female rhesus monkeys were investigated. After confirmed ovulation, four adult female rhesus monkeys were treated during the following cycle with 4 mg/kg/day of HCB, and four other monkeys were treated with the same dose of Clophen A 30. Ovulation was blocked in three PCB-treated and one HCB-treated monkeys. Whereas the levels of luteinizing hormone and follicle-stimulating hormone did not seem to be changed directly by the treatment, low estrogen levels were found during the anovulatory cycles. Studies with PCB- and HCB-treated superovulated rats indicated interaction of the chemicals with ovarian steroidogenesis. Altered hepatic steroid metabolism may also cause low estrogen levels in treated animals.

Animals↗