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Effects of the cannabinoid CB1 receptor agonist CP55,940 and antagonist SR141716A on d-amphetamine-induced behaviours in Cebus monkeys.

Several clinical studies have shown that alterations in the cannabinoid system in the brain may be associated with schizophrenia. Although evidence points towards an antipsychotic potential for cannabinoid antagonists, experimental studies have shown inconsistent behavioural effects of cannabinoid ligands within and across species. The aim of the present study was to explore these contradictory findings in a non-human primate model, predictive of antipsychotic efficacy in humans. The effects of the cannabinoid CB1 receptor antagonist SR141716A and the CB1 receptor agonist CP55,940 were explored in an d-amphetamine-based Cebus monkey model of psychosis. The monkeys were sensitive to extrapyramidal side effects (EPS), and the side-effect profiles of the drugs were explored as well. SR141716A (0.1, 0.25, 0.375, 0.5 and 0.75 mg/kg) and CP55,940 (0.0025, 0.005 and 0.01 mg/kg) were administered by subcutaneous injection alone and in combination with d-amphetamine (0.25mg/kg). SR141716A (0.1-0.5mg/kg) reduced d-amphetamine-induced arousal, while CP55,940 had no significant effect upon d-amphetamine-induced behaviours. No EPS were observed with either of these compounds. These data suggest that cannabinoid CB1 antagonists such as SR141716A may have limited antipsychotic potential in man as to positive symptoms. SR141716A administered alone induced anxiolytic-like behaviour, whereas administration of CP55,940 alone showed anxiogenic properties.

Animals↗

A natural asymptomatic herpes B virus infection in a colony of laboratory brown capuchin monkeys (Cebus apella).

Herpes B virus (BV) infection of macaques persists in the natural host, but is mainly asymptomatic. However, BV can cause fatal disease in humans and in several non-macaque species such as capuchin monkeys (Cebus apella). The BV infection described here in a colony of capuchin monkeys was persistent but asymptomatic. Initially the infection was detected serologically in five out of seven animals. However, using polymerase chain reaction (PCR) developed specifically for BV, we found the virus in all seven clinically healthy animals. It is probable that the infection was transferred from BV-infected macaques housed in different cages but in the same room for several years. We have no evidence to indicate that similar asymptomatic infections may occur in other New World species but the possibility should not be discounted. We recommend that the housing of capuchin monkeys in close proximity to macaques should be avoided and that greater caution should be used when handling capuchin monkeys and possibly other New World species that have been in contact with macaques. All may act as a source of BV infection in humans, hence routine, repeated testing of all primates is essential.

Animal Technicians↗

Primary structure of adult hemoglobin of white-throated capuchin, Cebus capucinus.

The alpha and beta chains of White-Throated Capuchin (Cebus capucinus) hemoglobin were separated and digested by trypsin. The tryptic peptides were isolated and sequenced by conventional methods. The peptides in each chain were aligned by the homology of their sequences with those of human adult hemoglobin. The primary structures thus deduced are compared with those of other primate hemoglobins, and we discuss the molecular evolution of hemoglobins, in particular the rate of evolution in New World monkey hemoglobins.

Amino Acid Sequence↗

Two-dimensional map of direction selectivity in cortical visual area MT of Cebus monkey.

We studied the spatial organization of direction of motion in visual area MT of the Cebus apella monkey. We used arrays of 6 (700 micro m apart) parallel electrodes in penetrations tangential to the cortical layers to record multi-unit responses to moving bars, at 200 micro m steps. We determined the direction selectivity at each recording site. The data from single penetrations showed cyclic and gradual changes in the direction selectivity of clusters of cells, intermixed with abrupt 180 degrees discontinuities along the electrode track. In order to obtain maps of direction of motion selectivity, we examined the spatial distribution of direction of motion in MT and we applied a method to determine the location of the centers of radial arrangements of direction selectivity. This tangential organization is characterized by slow continuous changes in direction of motion, interrupted by discontinuities. The changes in direction selectivity are organized radially in a pinwheel fashion and in slabs of linear variation. The pinwheel arrangements have 800-1400 micro m in diameter. The size of the radial arrangement is comparable to the point image size in area MT at each eccentricity.

Animals↗

Correlative scanning and transmission electron microscopic study on the ependymal surface of Cebus apella.

Topographical variations of the ependymal surface of the whole brain ventricular system of Cebus apella, a wild Brazilian species, were studied at the scanning electron microscope after CO2 critical point drying and carbon-gold coating. Certain selected areas were also studied at the transmission electron microscope, following standard technical procedures. We observed distinct patterns in the distribution of cilia, microvilli, other cell projections, and the so called supraependymal structures. Based on the morphological findings, functional considerations are made.

Animals↗

Morphology of the walls of the cavernous sinus of Cebus apella (tufted capuchin monkey).

The morphology of the dura mater and its relationship with the structures of the cavernous sinus were analyzed in five tufted capuchin monkeys (Cebus apella) using histological sections, showing that the walls of the cavernous sinus of this species are similar to those of other primates, including man. Except for the medial wall of the cavernous sinus, the remaining walls consist of two distinct dura mater layers. The deep layer of the lateral wall of the cavernous sinus is contiguous to the sheath of the oculomotor, trochlear and ophthalmic nerves. Arterioles, venules, venous spaces, neuronal bodies and nervous fiber bundles are found on this lateral wall.

Animals↗

Chronic myocardial damage in experimental T. cruzi infection of a New World primate, Cebus sp. monkey.

Eighteen Cebus apella monkeys, (juvenile and adult of both sexes) were inoculated five years ago, with three Trypanosoma cruzi strains (CA1, n = 10; Colombian, n = 4 and Tulahuen, n = 4), either by conjunctival or intraperitoneal route, once or repeatedly. Parasitological, hematological, serological, enzymatic, radiographic, electro and echocardiographic findings have been previously published and they are similar to those observed in human pathology. The most frequent electrocardiographic alteration was right branch bundle block. Six animals, chosen at random, were sacrificed. Those sacrificed 20 to 25 months post-first inoculation showed focal accumuli of leukocytes with myocytolysis. Foci of diffuse interstitial fibrosis with mild infiltrate of leukocytes among fibers were observed in the animals sacrificed 36 to 47 months post-inoculation. No parasites were seen. The lesions were more prominent in the ventricular walls and the septum. The fact that the infiltrates were predominant in the animals sacrificed at a shorter time after first inoculation and that fibrosis was more severe in those sacrificed at a longer time suggests that there is a progression of the infiltrative lesions to fibrosis, with a leukocytic activity indicative of a chronic phase. These lesions are similar to those described in human chronic Chagas' disease. This would demonstrate that this model is useful in evaluating a progress in the knowledge of the pathogenesis which is still a controversial issue, immunology, immunogenesis and chemotherapeutic agents of the chronic and indeterminate phases of this disease.

Animals↗

[Experimental cutaneous leishmaniasis. III. Histopathological aspects of the developmental behavior of the cutaneous lesion induced in Cebus apella (Primates: Cebidae) by Leishmania (Viannia) lainsoni, L. (V.) braziliensis and L. (Leishmania) amazonensis].

We have studied the histopathological aspects related to the evolution of cutaneous lesions experimentally produced in the monkey Cebus apella (Primates: Cebidae) by Leishmania (V.) lainsoni, L. (V.) braziliensis and L. (L.) amazonensis. Microscopical examination of a series of biopsies obtained from these animals showed the kinetics of the cutaneous lesions regarding three species of Leishmania inoculated, as follows: 1) an initial non-specific chronic inflammatory infiltrate; 2) macrophagic nodules; 3) necrosis of parasitized phagocytic cells; 4) epitheliode granuloma; 5) absorption of the necrotic area (sometimes forming "foreign-body granuloma"); 6) a non-specific residual inflammatory infiltration; and 7) cicatrization. These pathological processes are, of course, responsible for both development and resolution of the leishmaniotic lesion. We also discuss some immunopathological mechanisms probably related with the sequential events, and that could be also responsible for the different clinical aspects found in man.

Animals↗

Schistosoma mansoni: preclinical studies with 9-Acridanone-hydrazones in Cebus monkeys experimentally infected.

Derivatives of acridine (9-Acridanone-hydrazones) were tested in Cebus monkeys experimentally infected with Schistosoma mansoni, at the dosages of 50, 25, and 12.5 mg/kg (p.o., single dose). At least, four compounds seemed to be very promising, promoting alterations in the oogram and reducing the worm burden drastically, even at the lowest dose (12.5 mg/kg). No side effects could be detected after drug administration.

Acridines↗

Gastric acid secretion response in the Cebus apella. A monkey model of chronic Chagas' disease.

The objective was to study the secretory pattern, both basal and stimulated either by histamine (0.1 mg/kg) or pentagastrin (64 micrograms/kg) in eighteen Cebus apella monkeys chronically infected with different T. cruzi strains (CA1, n = 10; Colombian, n = 4 and Tulahuen, n = 4) and to describe the morphological findings in the gastrointestinal tract in twelve infected (6 sacrificed and 6 spontaneously dead) and four healthy monkeys. All infected monkeys and 35 healthy ones were evaluated by contrast X-ray examination. No differences were observed in basal acid output between control and infected groups. Animals infected with the Tulahuen and Colombian strains showed significant lower values of peak acid output in response to histamine or pentagastrin (p < 0.01 and p < 0.05 respectively; "t" test) in comparison to the controls. Barium contrast studies showed enlargement and dilatation of the colon in three infected animals. Histopathological lesions were seen in 75% of the autopsied animals either in colon alone (33%) or both, in colon and esophagus (42%). The normal secretion observed in the CA1 infected group could be due to a lower virulence of the strain, a lower esophageal tropism or the necessity of a longer post-infection time to cause lesions.

Animals↗

Plasmid profile in oral Fusobacterium nucleatum from humans and Cebus apella monkeys.

Fusobacterium nucleatum is a strict anaerobe and is indigenous of the human oral cavity. This organism is commonly recovered from different monomicrobial and mixed infections in humans and animals. In this study, the plasmid profile, the plasmid stability and the penicillin-resistance association in oral F. nucleatum isolated from periodontal patients, healthy subjects and Cebus apella monkeys were evaluated. Forty-five F. nucleatum strains from patients, 38 from healthy subjects and seven from C. apella were identified and analyzed. Plasmid extraction was performed in all the isolated strains. These elements were found in 26.7% strains from patients and one strain from C. apella. Strains from healthy subjects did not show any plasmid. Most of strains showed two plasmid bands ranging from 4 to 16 Kb, but digestions with endonucleases showed that they belonged to a single plasmid. The plasmid profile was similar and stable in human and monkey strains. Also, plasmids were classified into three groups according to size. Two strains were positive to beta-lactamase production and no plasmid DNA-hybridization with a beta-lactamase gene probe was observed, suggesting a chromosomal resistance.

Adult↗

[Experimental skin leishmaniasis: II--course of the infection in the Cebus apella primate (Cebidae) caused by Leishmania (V.) braziliensis and L. (L.) amazonensis].

As a means of assessing the usefulness of the monkey Cebus apella as an experimental model for the study of cutaneous leishmaniasis, 5 of these animals were inoculated intradermally at 8 sites along the tail with 3 X 10(6) promastigotes of L. (V.) braziliensis, while a further 5 monkeys received similar inoculations with 3 X 10(6) promastigotes of L. (L.) amazonensis. Following the inoculations, weekly examinations and monthly biopsies showed evolution of resulting skin lesions to be as follows: a) L. (V.) braziliensis: lesions were first visible 15-20 days post-inoculation (p.i), and at 30 days they were clearly of an erythematous-papular nature, which assumed a nodular form at 60 days; after 3 months a spontaneous ulceration of these lesions was noted and, at 4 months, the initiation of healing. In one animal total healing was apparent 5 months p.i; in two others at 6 months, in another monkey after 7 months, and in the last animal at 10 months p.i. Amastigotes were demonstrated in smears from the lesions of all monkeys up to 90 days p.i; up to 120 days in two animals, and at 180 days p.i. in the monkey which showed resolution of the lesions after 10 months. b) L. (L.) amazonensis lesions were first apparent after 20 days p.i; at 30 days they were of an erythematous-papular nature, developing into nodules at 60 days. From the third month of infection onwards, however, the lesions diminished rapidly and, at 90 days p.i. amastigotes were no longer detectable in the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[The experimental infection of Cebus apella sp. monkeys with Trypanosoma cruzi. Its clinical, electrocardiographic and anatomicopathological assessment].

Thirty-two monkeys were captured and adapted to laboratory conditions captives isolated. They were submitted to multiple xenodiagnosis which were negative. Twelve were infected intraperitoneally with different strains of T. cruzi (1.10(5) to 5.10(6)). Twenty were the control group. Between on to six years both the control group and the infected monkeys, were submitted to xenodiagnosis, serological testing clinical examination and electrocardiography. The clinical examination and the electrocardiogram were always normal. The monkey were autopsied and histological examination detected in the infected group four monkeys with evidence of disease: one with parasites in the tissue and three with chronic myocarditis. Parasitaemia was in 66.66% of the monkeys in the acute phase and the serology was positive in 91.66% in the chronic phase. The authors concluded that Cebus monkeys were not susceptible to the development of the disease but they could be utilized to maintain of such strains and studies of serological research in long-terms infections.

Animals↗

Antischistosomal activity of acridanone-hydrazones in Cebus monkeys experimentally infected with the SJ strain of Schistosoma mansoni.

In this study, four compounds were utilized at the dose of 12.5 mg/kg body weight, p.o., to treat Cebus monkeys experimentally infected with about 200 cercariae of Schistosoma mansoni (SJ strain), via transcutaneous route. The oograms performed with rectal snips, as well as stool examinations carried out periodically, showed no viable eggs of the parasite, from day 29 to 226 post-treatment. The perfusion undertaken after killing the animals showed absence of worms in the treated monkeys, whereas 83 worms were recovered from the control, thus corroborating the results obtained by means of oograms and coproscopy. These results confirm the efficacy of 9-acridanone-hydrazones previously tested against the LE strain of S. mansoni. The low curative dose and apparent absence of toxicity render these drugs an important therapeutic reserve, taking into consideration the reports on the resistance of S. mansoni to the modern drugs oxamniquine and praziquantel.

Acridines↗

Chronic experimental infection by Trypanosoma cruzi in Cebus apella monkeys.

Twenty young male Cebus apella monkeys were infected with CA1 Trypanosoma cruzi strain and reinfected with CA1 or Tulahuen T. cruzi strains, with different doses and parasite source. Subpatent parasitemia was usually demonstrated in acute and chronic phases. Patent parasitemia was evident in one monkey in the acute phase and in four of them in the chronic phase after re-inoculations with high doses of CA1 strain. Serological conversion was observed in all monkeys; titers were low, regardless of the methods used to investigate anti-T. cruzi specific antibodies. Higher titers were induced only when re-inoculations were performed with the virulent Tulahuén strain or high doses of CA1 strain. Clinical, electrocardiographic and ajmaline test evaluations did not reveal changes between infected and control monkeys. Histopathologically, cardiac lesions were always characterized by focal or multifocal mononuclear infiltrates and/or isolated fibrosis, as seen during the acute and chronic phases; neither amastigote nests nor active inflammation and fibrogenic processes characteristic of human acute and chronic myocarditis respectively, were observed. These morphological aspects more closely resemble those found in the "indeterminate phase" and contrast with the more diffuse and progressive pattern of the human chagasic chronic myocarditis. All monkeys survived and no mortality was observed.

Animals↗

Cebus apella (Primata: Cebidae) as a new host for Fonsecalges johnjadini (Acari: Psoroptidae, Cebalginae) with a description of anatomopathological aspects.

Mites collected from the auditory canal of Cebus apella (capuchin monkey), family Cebidae, were identified as Fonsecalges johnjadini (Psoroptidae, Cebalginae). It is the first record of this parasite from this monkey. This paper emphasizes the importance of clinical and anatomopathological examinations for parasitic diagnosis in wild animals.

Animals↗

Horizontal projections of area 17 in Cebus monkeys: metric features, and modular and laminar distribution.

Metric features and modular and laminar distributions of intrinsic projections of area 17 were studied in Cebus apella. Anterogradely and retrogradely labeled cell appendages were obtained using both saturated pellets and iontophoretic injections of biocytin into the operculum. Laminar and modular distributions of the labeled processes were analyzed using Nissl counterstaining, and/or cytochrome oxidase and/or NADPH-diaphorase histochemistry. We distinguished three labeled cell types: pyramidal, star pyramidal and stellate cells located in supragranular cortical layers (principally in layers IIIa, IIIb alpha, IIIb beta and IIIc). Three distinct axon terminal morphologies were found, i.e., Ia, Ib and II located in granular and supragranular layers. Both complete and partial segregation of group I axon terminals relative to the limits of the blobs of V1 were found. The results are compatible with recent evidence of incomplete segregation of visual information flow in V1 of Old and New World primates.

Animals↗

Changes of ongoing activity in Cebus monkey perirhinal cortex correlate with behavioral performance.

A Cebus apella monkey weighing 4 kg was trained in a saccadic eye movement task and while the animal performed the task we recorded the extracellular activity of perirhinal cortical neurons. Although the task was very simple and maintained at a constant level of difficulty, we observed considerable changes in the performance of the monkey within each experimental session. The behavioral states responsible for such variation may be related to arousal, motivation or attention of the animal while engaged in the task. In approximately 20% (16/82) of the units recorded, long-term direct or inverse correlations could be demonstrated between the monkey's behavioral state and the cells' ongoing activity (independent of the visual stimulation or of the specific behavior along a trial). The perirhinal cortex and other medial temporal structures have long been associated with normal memory function. The data presented here were interpreted in terms of recent reports focusing on the subcortical afferents to temporal lobe structures and their possible role in controlling arousal, motivation, or attention.

Animals↗