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PubMed1989

Seasonal or ecological differences in diet and molar microwear in Cebus nigrivittatus.

Dental microwear analyses have raised new hopes and questions for functional morphologists. One hope is that analyses will allow insights into subtle dietary differences of extinct species. One major question is whether seasonal and/or habitat differences in dental microwear are reliably detectable. The extensive collections of Cebus nigrivittatus obtained by the Smithsonian Venezuelan Project allowed us to examine seasonal and habitat differences in dental microwear. Specimens were collected from three distinct ecological life zones that are distinguished by both the amount of rainfall and its seasonability. Environmental variation is generally correlated with variation in resource availability which, in C. nigrivittatus, affects diet. Published field studies indicate that these animals depend more on dry hard fruit and chitinous invertebrates during drier times and succulent fruits and caterpillars during wetter times of the year. As in previous microwear analyses, epoxy replicas were prepared from dental impressions, and the replicas were examined under a scanning electron microscope. Two micrographs were taken of facet 9 on M2 of each specimen. Mean values for the proportion of pits (vs. scratches), pit width, and scratch width were computed for each of 62 individuals and compared between ecological zones and collecting dates by using a multiple comparison test. Results indicate that, while seasonal differences in molar microwear in C. nigrivittatus are perhaps reliably detectable, 1) they are small in magnitude, 2) they are only detectable in certain ecological life zones, and 3) they are not of the order of magnitude that will obscure major interspecific differences in molar microwear such as those between C. apella and C. nigrivittatus.

Analysis of Variance↗
PubMed1991

Morphometric analysis of craniofacial growth in Cebus apella.

The present study was undertaken to provide a quantitative description of craniofacial growth in Cebus apella in three dimensions. Landmarks from a cross-sectional sample of sexed and dentally aged crania were collected using a 3Space digitizer. Two methods of three-dimensional form analysis, euclidian distance matrix analysis (EDMA) and finite-element scaling analysis (FESA), were used to investigate growth changes in the cranium. Male and female growth was examined by comparing the youngest male mean form to all other age/sex specific mean forms. In addition, form differences between the sexes were studied by comparing male and female mean forms at each age. The cranium was divided into four regions for analysis: muzzle, upper face, neurocranium, and basicranium. Growth changes within each region were examined. In the muzzle and neurocranium, most growth occurs along the anteroposterior axis. Growth around pterion and the lower orbital rim is prominent within the upper face. The basicranium shows a surprisingly large amount of form change with growth. This form change is due to the mediolateral expansion of the basioccipital, and to the posterior migration and inferior rotation of basion. Males and females have similar growth patterns, but males tend to be larger than females in nearly all dimensions at every developmental age except the youngest. Evidence suggests that craniofacial sexual dimorphism is primarily due to males growing faster than females for approximately the same amount of time.

Animals↗
PubMed2003

Urocortin in the central nervous system of a primate (Cebus apella): sequencing, immunohistochemical, and hybridization histochemical characterization.

The urocortin (UCN)-like immunoreactivity and UCN mRNA distribution in various regions of the nonprimate mammalian brain have been reported. However, the Edinger-Westphal nucleus (EW) appears to be the only brain site where UCN expression is conserved across species. Although UCN peptides are present throughout vertebrate phylogeny, the functional roles of both UCN and EW remain poorly understood. Therefore, a study focused on UCN system organization in the primate brain is warranted. By using immunohistochemistry (single and double labeling) and in situ hybridization, we have characterized the organization of UCN-expressing cells and fibers in the central nervous system and pituitary of the capuchin monkey (Cebus apella). In addition, the sequence of the prepro-UCN was determined to establish the level of structural conservation relative to the human sequence. To understand the relationship of acetylcholine cells in the EW, a colocalization study comparing choline acetyltransferase (ChAT) and UCN was also performed. The cloned monkey prepro-UCN is 95% identical to the human preprohormone across the matched sequences. By using an antiserum raised against rat UCN and a probe generated from human cDNA, we found that the EW is the dominant site for UCN expression, although UCN mRNA is also expressed in spinal cord lamina IX. Labeled axons and terminals were distributed diffusely throughout many brain regions and along the length of the spinal cord. Of particular interest were UCN-immunoreactive inputs to the medial preoptic area, the paraventricular nucleus of the hypothalamus, the oral part of the spinal trigeminal nucleus, the flocculus of the cerebellum, and the spinal cord laminae VII and X. We found no UCN hybridization signal in the pituitary. In addition, we observed no colocalization between ChAT and UCN in EW neurons. Our results support the hypothesis that the UCN system might participate in the control of autonomic, endocrine, and sensorimotor functions in primates.

Amino Acid Sequence↗
PubMed2003

Three streams of visual information processing in V2 of Cebus monkey.

Gattass and collaborators (Gattass R, Rosa MGP, Souza APB, Piñon MCG, Neuenschwander S [1990a] Braz J Med Biol Res 23:375-393) proposed that the dorsal stream of visual processing, as defined by Ungerleider and Mishkin (Ungerleider LG, Mishkin M [1982] In: Ingle DJ, Goodale MA, Mansfield RJW, editors. Analysis of visual behavior. Cambridge: Massachusetts Institute of Technology. p 549-586), can be subdivided into dorsolateral and dorsomedial streams, and suggested that they may be involved in different aspects of the processing of motion and spatial perception, respectively. The goal of the present study was to provide additional evidence for this hypothesis by using cytochrome oxidase immunohistochemistry combined with retrograde tracing techniques. In Old World monkeys, the locations of visual area 4 (V4; ventral stream) and middle temporal area (MT; dorsal stream) projecting neurons in V2 supports the hypothesis that the cytochrome oxidase (CytOx)-rich thin stripes and the CytOx-poor interstripes are associated with the ventral stream, and that the CytOx-rich thick stripes belong to the dorsal stream. In this study we describe, in the New World monkey Cebus, the distribution of retrogradely labeled cells in V2 relative to the CytOx compartments after fluorescent tracers were placed in areas V4, MT, and the parietooccipital area (PO). We found PO-projecting neurons in CytOx-rich thick stripes and CytOx-poor interstripes in V2, whereas MT-projecting neurons appeared almost exclusively in thick stripes. In contrast, V4-projecting neurons were located mostly in CytOx-poor interstripes and CytOx-rich thin stripes. In addition, V4- and MT-projecting neurons were located mainly in supragranular layers, whereas PO-projecting neurons were located in supragranular and infragranular layers. These results support the hypothesis for the existence of three distinct streams of visual processing: ventral (including V4), dorsolateral (including MT), and dorsomedial (including PO).

Animals↗
PubMed1988

Representation of the visual field in the second visual area in the Cebus monkey.

The representation of the visual field in the second visual area (V2) was reconstructed from multiunit visual responses and anatomical tracers. Receptive field plotting was performed during multiple recording sessions in seven Cebus apella monkeys under N2O/O2 and immobilized with pancuronium bromide. V2 forms a continuous belt of variable width around striate cortex (V1) except at the most anterior portion of the calcarine sulcus. In each hemisphere V2 contains a visuotopic representation of the contralateral visual hemifield. The representation of the vertical meridian is adjacent to that of V1 and forms the posterior border of V2. The representation of the fovea of V2 is adjacent to that of V1. The representation of the horizontal meridian (HM) is continuous with that of V1; then it splits to form the anterior border of V2, both dorsally and ventrally. The lower quadrant of the visual field is represented dorsally and the upper quadrant ventrally. The visual topography of V2 is coarser than that of V1. In V2, receptive fields corresponding to recording sites separated by a cortical distance of up to 4 mm may represent the same portion of the visual field. In three additional animals, combined injections of fluorescent tracers along the HM representation in V1 yielded two projection sites at the anterior border of V2. The split of the HM representation is estimated to occur at an eccentricity below 1 degree. Quantitative analysis showed that in V2 the representation of the central visual field is magnified relative to that of the periphery. The cortical magnification factor is greater along the isopolar dimension than along the isoeccentric one. Receptive field size in V2 increases with increasing eccentricity. In sections stained for myelin by the Heidenhein-Wöelcke method V2 can be distinguished from the surrounding cortex for most of its extent.

Animals↗
PubMed1988

Nerve growth factor receptor immunoreactivity in the nonhuman primate (Cebus apella): distribution, morphology, and colocalization with cholinergic enzymes.

A monoclonal antibody raised against the receptor for nerve growth factor (NGF) was used to examine the distribution and morphology of NGF receptor-containing neurons within the central nervous system of Cebus apella monkeys. Most somata demonstrating positive immunoreactivity were localized within the Ch1-4 regions of the basal forebrain. Neurons in the Ch1 region displayed morphological features typical of cholinergic medial septal neurons. These perikarya were primarily vertically oriented (40-50 micron along the vertical axis) with both apical and basal neuritic processes. Magnocellular (40-50 micron) neurons within the Ch2 (vertical limb of the diagonal band), Ch3 (horizontal limb of the diagonal band) and Ch4 (nucleus basalis of Meynert) regions were multipolar and had rounded perikarya that often displayed an eccentric nucleus. Fibers presumably originating from the Ch1-2 regions were observed throughout the fimbria-fornix system and were found to terminate preferentially within the CA1 and CA3 regions of the hippocampal formation and within the dentate gyrus of the hippocampus. An intense fiber network was also observed in the olfactory tubercle and other rhinencephalic structures, presumably originating from the Ch3 region of the basal forebrain. Beaded processes emanating from the Ch4 region primarily coursed within the external capsule and terminated preferentially within layers I, II, and IV of the cerebral cortex. In a pattern similar to that of cortical acetylcholinesterase (AChE) staining, NGF receptor immunopositive fibers were oriented in a tangential plane within the molecular layer of the cortex and in both a radial and tangential fashion within the cortical granular cell layers. In addition to neural innervation, there was an extensive vascular apposition by NGF receptor-containing neurites on both large caliber vessels and microcapillaries. NGF receptor immunoreactivity was extensively, but not exclusively, colocalized with choline acetyltransferase (ChAT) and AChE in the basal forebrain. A small population of cholinergic neurons were observed that were not NGF receptor-immunoreactive. Conversely, a few NGF receptor-containing neurons that were noncholinergic were also observed in this brain region. NGF receptor-containing somata were also identified in the putamen. The number of immunoreactive neurons observed in this structure, however, would not appear to be sufficient to account for the homologous NGF receptor binding densities described in rodents.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase↗
PubMed1991

Topographic organization of cortical input to striate cortex in the Cebus monkey: a fluorescent tracer study.

Cortical afferents to area V1 were studied in seven Cebus monkeys by means of retrograde fluorescent tracers. Injections were placed in V1, under electrophysiological guidance, in the regions of representation of both the upper and lower visual quadrants, at eccentricities that ranged from 0.5 to 64 degrees. In all cases retrogradely filled neurons were found in retinotopically corresponding portions of areas V2 and MT, as defined electrophysiologically (Rosa et al: J. Comp. Neurol. 275:326, 1988; Fiorani et al: J Comp Neurol 287:98, 1989). The results also revealed two other visual zones located anterior to V2 here named third and fourth visual areas. A topographical organization of the connections was observed in these areas, with upper quadrant located ventrally and lower quadrant located dorsally. A clear central-peripheral gradient, from the lateral to the medial cortical surface, was also observed in these areas. Lower field injections revealed crude topographic organization in area DZ and a diffuse projecting zone in the annectent gyrus. Peripheral injections in V1 revealed a clear upper and lower field segregation in areas PO and prostriata as well as a complex topography in MST. In addition, another region of labeling revealed the presence of an area, the temporal ventral posterior region, with an organized topographic representation of the upper field, with a central to peripheral gradient, from the lateral to the medial cortical surface. Three groups of cortical areas were distinguished according to the laminar distribution of neurons labeled from V1. In the first group, which is characterized by dense infra- and supragranular labeling, only V2 was included. The second group consists of areas V3, MT, and PO. These areas show dense labeling in the infragranular layers and occasionally sparse labeling in the supragranular layers. Finally, V4 and the other projecting areas, which are characterized by exclusive labeling of the infragranular layers were included in the third group.

Afferent Pathways↗
PubMed1994

Identification and visuotopic organization of areas PO and POd in Cebus monkey.

Two visual areas of the anterior bank of the parietooccipital sulcus, areas PO and POd, were identified and their visual field representations were studied in six anesthetized and paralyzed Cebus monkeys. The definition of these areas was based on electrophysiological mapping and myeloarchitecture. PO is located in the ventral aspect of the anterior bank of the parietooccipital sulcus and ventral precuneate gyrus. It borders area V2 posteriorly and ventrally in the depth of the parietooccipital sulcus, area V3d laterally, and another undescribed visual area medially. POd was located dorsal to area PO and ventral to architectonic area PE. The representations of the visual field in areas PO and POd are complex. In each hemisphere, these areas have a virtually complete representation of the contralateral visual hemifield. Different from the previously described visual areas, in PO and POd there is a precise organization of isopolar lines and a complex organization of the isoeccentric ones. In PO, as well as in POd, the representation of the horizontal meridian runs dorsoventrally along the parietooccipital sulcus. The upper visual quadrant is represented medially and the lower visual quadrant laterally. A large and complex representation of the periphery, from 20 degrees to 60 degrees eccentricity is present at the lateral and medial portions of these areas. By contrast, the representation of the central 20 degrees is very small in both PO and POd. The central visual field is represented ventrally in PO and dorsally in area POd. Area POd shows a more stratified myeloarchitectonic pattern than PO and both areas can be distinguished from other surrounding areas by their heavier myelinated pattern.

Animals↗
PubMed1992

Regional changes in 2-deoxyglucose uptake associated with neuroleptic-induced tardive dyskinesia in the Cebus monkey.

The neural mechanisms that mediate a primate model of tardive dyskinesia have been investigated using the 2-deoxyglucose (2-DG) uptake technique. Three groups of Cebus monkeys were used. Some of the animals received long-term neuroleptic treatment. These animals were allotted to one of two groups depending on whether they developed tardive dyskinesia or not. A third group of animals served as untreated controls. The neuroleptic-treated dyskinetic animals showed reduced uptake of 2-DG in the medial segment of the globus pallidus and in the ventral anterior (VA) and ventral lateral (VL) nuclei of the thalamus relative to that seen in the equivalent structures in the neuroleptic-treated nondyskinetic and untreated control animals. The data are interpreted as suggesting that tardive dyskinesia is mediated by underactivity of the pathways from the subthalamic nucleus to the medial pallidal segment and the substantia pars nigra pars reticulata, which in turn result in a loss of gamma-aminobutyric acid-ergic inhibition of the VA and VL thalamic nuclei. This suggests that tardive dyskinesia shares a common underlying neural mechanism with other hyperkinesias such as chorea and ballism.

Animals↗
PubMed2002

Individual and seasonal variation in fecal testosterone and cortisol levels of wild male tufted capuchin monkeys, Cebus apella nigritus.

This study tested the "challenge hypothesis" and rank-based predictions for temporal steroid production in male tufted capuchin monkeys, Cebus apella. Fecal samples (n = 209) collected from six wild males were analyzed for testosterone and cortisol concentration by enzyme immunoassay. The temporal pattern in male steroid production was compared to female sexual activity and rates of male aggression. The top-ranking adult male did not differ from other adult males in testosterone or cortisol concentration. Mean adult testosterone was significantly higher than mean subadult testosterone throughout the year. There was a clear elevation of testosterone and cortisol in both adult and subadult males during the peak of adult female sexual activity after the birth season. In fact, the magnitude of increase in testosterone was higher than predicted for a species with low male-male aggression. However, there was no difference between nonbreeding baseline testosterone levels during the birth season, and the "breeding" baseline of testosterone in males found during asynchronous female sexual activity. Of all behavioral indices examined, the distribution of female-maintained consortships was the best predictor of mean adult male testosterone concentrations. Although in many species, elevated testosterone coincides with increased male-male aggression, in the present study, the sustained high-magnitude increase in steroids during the peak of adult female sexual activity was associated with a relatively low rate of male-male intragroup aggression.

Age Factors↗
PubMed1985

Behavioral effects of long-term neuroleptic treatment in Cebus monkeys.

Tardive dyskinesia (TD) occurs in predisposed individuals receiving neuroleptic treatment, but prior to the onset of symptoms it is not possible to predict who is at risk for this disorder. If the time course for evolving symptoms, perhaps mediated through dopamine hypersensitivity, could be identified, treatment interventions could be initiated. Eight male Cebus monkeys (15-18 years old) were tested with the dopamine agonists apomorphine, d-amphetamine, bromocriptine, and pergolide before, during, and after 3 months of treatment with haloperidol 0.25 mg/kg daily PO. This treatment cycle was repeated four times. Apomorphine and amphetamine produced moderate buccolinguo-masticatory (BLM) signs. Bromocriptine and pergolide produced very few BLMs. Initially haloperidol suppressed dopamine agonist-induced BLMs, but tolerance to the effect developed and was replaced by a potentiation of apomorphine-induced BLMs. Markedly increased apomorphine- and amphetamine-induced BLMs were seen following the first 3 months of haloperidol medication (behavioral hypersensitivity), but this gradually decreased to near-baseline levels, even with re-exposure to neuroleptics in the four treatment cycles. Bromocriptine and pergolide produced no signs of BLM behavioral hypersensitivity. These findings suggest that long-term neuroleptic treatment in nonhuman primates induces dynamic compensatory CNS changes, which may not fully explain the pathogenesis of TD on the basis of dopamine hypersensitivity.

Animals↗
PubMed1985

Induction of tardive dyskinesia in Cebus apella and Macaca speciosa monkeys: a review.

Two different studies were performed in subhuman primates in an attempt to induce symptoms of tardive dyskinesia. The first study lasted for over 5 years. This involved elderly Macaca speciosa. The animals were given first 25 mg of fluphenazine decanoate and later the enanthate IM (3.2 mg/kg) every 2 weeks and on 5 days a week, haloperidol, first IM and later PO. Haloperidol was given first in doses of 1.0 mg/kg and ultimately after years of therapy, in doses of 6.4 mg/kg per day. Those animals who survived gained weight to over 10 kg. After neuroleptic withdrawal, tardive dyskinesia became evident in 1 month. The symptoms of tardive dyskinesia following cessation of medication lasted a maximum of 1 year. This animal model produced very impressive symptoms in one of the three animals treated who survived. This is not a very practical animal model from the aspects of economics (costly), time (5 years), and animal availability (rare and endangered species). However, the symptoms of tardive dyskinesia are very striking and identical with human tardive dyskinesia in a susceptible animal. A more practical experimental animal model involved Cebus apella. Depot fluphenazine (0.1 to 3.2 mg/kg) was given continuously every 2 weeks for 1 year. In this species the symptoms of tardive dyskinesia became progressively prolonged and intense with each course of fluphenazine therapy and withdrawal, suggesting that reversible tardive dyskinesia may turn into irreversible tardive dyskinesia. With each succeeding course of fluphenazine therapy (1 month) and withdrawal (1-3 months), the animals appeared to be sensitized to both the acute extrapyramidal and the tardive dyskinesia symptoms. These animals were also given various experimental drug treatments including biperiden lactate, benztropine mesylate, and d-amphetamine after they developed signs of tardive dyskinesia.

Animals↗
PubMed1988

GABA agonists in cebus monkeys with neuroleptic-induced persistent dyskinesias.

Tetrahydroisoxazolopyridinol (THIP), a GABA receptor agonist, gamma-acetylenic-GABA(GAG) and gamma-vinyl-GABA(GVG), two GABA transaminase inhibitors were given in single parenteral doses to three Cebus apella monkeys with persistent dyskinetic movements induced by earlier long-term administration of haloperidol. High doses of THIP temporarily abolished dyskinesias but also caused bradykinesia, ataxia, dystonia and myoclonic jerks. GAG and GVG reduced dyskinesias to a lesser extent and with fewer side effects. Whether the observed antidyskinetic effect is secondary to the concomitant general toxic effects or if these drugs have a specific antidyskinetic action remains an open question.

4-Aminobutyrate Transaminase↗
PubMed1988

Ultrastructure of the meninges at the site of penetration of veins through the dura mater, with particular reference to Pacchionian granulations. Investigations in the rat and two species of New-World monkeys (Cebus apella, Callitrix jacchus).

At the sites where a vein penetrates through the dura mater, two aspects deserve particular attention: (i) The delineation of the perivascular cleft, a space belonging to the interstitial cerebrospinal fluid (CSF) compartment, toward the interior hemal milieu of the dura mater. (ii) The relationship between the perivascular arachnoid layer and the subdural neurothelium at the point of vascular penetration. These problems were investigated in the rat and in two species of New-World monkeys (Cebus apella, Callitrix jacchus). Concerning the first aspect, tight appositions of meningeal cells to the vessel wall, the basal lamina of which is widened and enriched with microfibrils, prevent communication between the interstitial CSF in the perivascular cleft and the hemal milieu in the dura mater. With reference to the second aspect, the perivascular arachnoid cells are transformed into neurothelial cells at the point where they become exposed to the hemal milieu of the dura mater and subsequently continuous with the subdural neurothelium. Leptomeningeal protrusions encompassing outer CSF space can penetrate into the dura mater. These protrusions may expand and branch repeatedly, forming along the wall of the dural sinus Pacchionian granulations. At these sites, however, the structural integrity of the sinus wall and the Pacchionian granulation is not lost. Numerous vesiculations not only in the sinus and vascular walls, but also in the cellular arrays of the Pacchionian granulations or paravascular leptomeningeal protrusions indicate mechanisms of transcellular fluid transport. Moreover, the texture of the leptomeningeal protrusions favors an additional function of these structures as a "volume" buffer.

Animals↗
PubMed1990

Afferents of the caudal fastigial nucleus in a New World monkey (Cebus apella).

The afferents of the fastigial nucleus (FN) were studied in two capuchin monkeys (Cebus apella) one of which had received a unilateral injection of horseradish peroxidase in the caudal FN, and a second monkey which received a control injection that involved the lateral caudal FN but extended into the cerebellar white matter between the FN and posterior interposed nucleus (PIN). All of the sources of FN afferents were found to be labeled bilaterally. In addition to the restricted distribution of labeled Purkinje cells in lobules VI and VII of the posterior lobe vermis ("oculomotor vermis"), retrogradely labeled cells were present in the dorsolateral pontine nucleus (DLPN), dorsomedial pontine nucleus (DMPN), nucleus reticularis tegmenti pontis (NRTP), pontine raphe (PR), paramedian nucleus reticularis pontis caudalis (NRPC), nucleus prepositus hypoglossi (NPH), subnucleus b of the medial accessory olivary nucleus (sbMAO), and vestibular complex (VC). The second (control) injection appeared to confirm a proposed (Langer et al. 1985b) projection from the flocculus to the basal interstitial nucleus. The results are discussed in terms of the functional relationships of the FN to the frontal eye field and oculomotor-related brainstem structures involved in the production of saccadic and smooth pursuit eye movements.

Afferent Pathways↗
PubMed1985

Effects of apomorphine and haloperidol on "spontaneous" stereotyped licking behaviour in the Cebus monkey.

Three recently arrived drug naive Cebus apella monkeys with "spontaneous" stereotyped oral movements were treated with apomorphine and haloperidol using a wide dose range. Low doses of apomorphine (0.05-0.1 mg/kg) suppressed the oral stereotypies without affecting normal behaviour such as grooming and scratching. Higher doses of apomorphine (0.25-1.0 mg/kg) and haloperidol (0.01-0.1 mg/kg) also decreased or abolished the oral stereotypies, but induced generalized stereotypies (apomorphine) or dystonia/parkinsonism (haloperidol), suppressing normal behaviour. The findings indicate that dopamine is involved in these presumably stress-induced (not drug-induced) stereotypies.

Animals↗
PubMed1993

Satellite DNA sequences in the New World primate Cebus apella Plaatyrrhini, Primates).

Two satellite DNAs, designated CapA and CapB, were isolated from the neotropical primate, Cebus apella. The satellites exhibit nonoverlapping distributions on C. apella chromosomes. CapA is a major component of interstitial regions of constitutive heterochromatin, a very large block of heterochromatin comprising most of the long arm of chromosome 11, and some telomeres. The CapA monomer has a length of about 1500 bp and appears recently to have undergone an amplification episode in the C. apella genome. CapA-like sequences are probably present in members of the family Cebidae (to which C. apella belongs), but not in members of the family Callitrichidae (marmosets). CapB sequences can be detected at the centromeres of many C. apella chromosomes, and similar sequences are present in all neotropical primates. The 342 bp CapB monomer shares 60%-64% sequence identity with several alpha satellite sequences of human origin. Because of its structure, sequence, and location, it appears that CapB is the New World primate homolog of Old World primate alpha satellite DNA.

Animals↗
PubMed1988

Suppression of neuroleptic-induced persistent abnormal movements in Cebus apella monkeys by enantiomers of 3-PPP.

Effects of the enantiomers of the dopamine (DA) autoreceptor agonist 3-PPP (0.5-8.0 mg/kg body weight, i.m.) were studied in three Cebus apella monkeys with persistent abnormal movements induced by prior long-term treatment with fluphenazine enanthate. In 2 of the animals, (-)-3-PPP abolished the abnormal movements while producing only negligible acute motor effects (trembling and stereotypy). (+)-3-PPP, administered to one of these monkeys, also produced a dose-dependent suppression of the persistent abnormal movements, along with the appearance of acute motor signs including tongue protrusions, hyperkinesia, and stereotypy; at the highest dose, there was a biphasic effect. In the first phase, there were pronounced acute motor signs but no persistent abnormal movements. In the second phase, there were neither acute nor persistent abnormal movements. One monkey was unaffected by (-)-3-PPP or low doses of (+)-3-PPP; a higher dose (4 mg/kg) produced hyperkinesia and increased persistent abnormal movements in one experimental setting. The suppression of neuroleptic-induced persistent abnormal movements by 3-PPP enantiomers may be related to their ability to act as autoreceptor agonists, while the acute motor signs produced by higher doses of (+)-3-PPP may be due to activation of postsynaptic DA receptors. The present findings suggest that (-)-3-PPP and drugs with a similar pharmacological profile might be effective as symptomatic treatments for tardive dyskinesia, with little chance of inducing acute extrapyramidal side-effects.

Animals↗