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At least 991 records · Page 55Linked to original sources
PubMed1997

Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor radioligand, 18F-fallypride in nonhuman primates using positron emission tomography.

We have investigated the ability of dopamine to compete with the binding of the high affinity dopamine D2 receptor positron emission tomography (PET) radioligand, 18F-fallypride. In vitro dissociation of 18F-fallypride with dopamine in rat striatal homogenates exhibited a dissociation rate, k(off), of 1.76 x 10(-2) min(-1) while the association rate constant, k(on), was found to be 5.30 x 10(8) M(-1) min(-1). This resulted in a dissociation constant, K(D) of 33 pM for 18F-fallypride. For in vivo studies, we investigated the effects of reserpine and d-amphetamine treatment on 18F-fallypride in an attempt to study competition of endogenous dopamine with the radioligand at the receptor sites in rats and monkeys. PET experiments with 18F-fallypride in two male rhesus monkeys were carried out in a PETT VI scanner. In control experiments, rapid specific uptake of 18F-fallypride in the striata was observed (0.05-0.06% injected dose (ID)/g) while nonspecifically bound tracer cleared from other parts of the brain. Striata/cerebellum ratios for 18F-fallypride were approximately 8 at 80 min postinjection, respectively. The monkeys received various doses (0.25 to 1.50 mg/kg) of d-amphetamine (AMPH) pre- and postinjection of the radioligand. There was a decrease of specifically bound 18F-fallypride as well as evidence of an enhanced clearance of specifically bound 18F-fallypride after administering AMPH in the two monkeys. The dissociation rates, k(off), of 18F-fallypride without AMPH was <10(-4) min(-1) but after 25 min preadministration of AMPH (1 mg/kg), it was 4.1 x 10(-3) min(-1) and after 17, 45 and 90 min postadministration of AMPH (1 mg/kg) it was 3.6 x 10(-3) to 4.0 x 10(-3) min(-1). Lower doses of AMPH (0.25 mg/kg) had a reduced effect on the binding of 18F-fallypride. No effect was seen until about 30 minutes after the injection of AMPH. Studies with various doses indicated that 18F-fallypride has a maximum response at doses of 0.75-1.50 mg/kg, with an approximately 16%/hour reduction in binding. These results indicate that AMPH stimulated release of endogenous dopamine reduces the specific binding of 18F-fallypride.

Animals↗
PubMed1999

Changes in striatal D2-receptor density following chronic treatment with amphetamine as assessed with PET in nonhuman primates.

Recent brain imaging studies suggest that schizophrenia may be related to abnormally high amphetamine-induced dopamine release. It is known that repeated use of amphetamine may cause paranoid psychosis and persisting stereotypies. The biochemical background for these signs and symptoms has not been clarified. In this study, positron emission tomography and [11C]raclopride were used to determine central D2-dopamine receptor density (Bmax) and apparent affinity (K(D)app) in Cynomolgus monkeys before and after 14 days of treatment with d-amphetamine sulphate (2 mg/kg/day; s.c.). One day after withdrawal from amphetamine, K(D)app was increased, suggesting [11C]raclopride competition with elevated concentration of dopamine. At 7 and 14 days after withdrawal, there was a 19-26% decrease in Bmax but no change in K(D)app as compared to baseline. Although this study was performed on two monkeys only, there was thus no support for the view that chronic intermittent hyperactivity of the dopamine system may be related to an upregulation of striatal D2-dopamine receptors. Repeated administration of amphetamine may, rather, cause a long-lasting downregulation of the D2-receptor density, which may be a neurochemical correlate to the abnormal movements, anhedonia, anxiety, and depression seen in psychostimulant abusers.

Amphetamine-Related Disorders↗
PubMed2000

In vitro and in vivo evaluation of the binding of the dopamine D2 receptor agonist (11)C-(R,S)-5-hydroxy-2-(di-n-propylamino)tetralin in rodents and nonhuman primate.

The in vitro autoradiographic binding characteristics as well as in vivo imaging characteristics of a dopamine D2 receptor agonist, (R, S)-2-(N-propyl-N-1'-(11)C-propyl)amino-5-hydroxytetralin ((11)C-5-OH-DPAT), were studied. In (3)H-spiperone assays using rat striata, 5-OH-DPAT exhibited an affinity of IC(50) = 2.5 nM. In vitro autoradiographs in rat brain slices with (11)C-5-OH-DPAT revealed selective binding to the dopaminergic regions in the striata which was displaceable by sulpiride. Varying concentrations of dopamine displaced this selective binding of (11)C-5-OH-DPAT to the striata in rat brain slices. This selective binding to the striata was also removed in the presence of the GTP analog, 5'-guanylylimidodiphosphate, indicative of the binding of (11)C-5-OH-DPAT to the high-affinity state of the D2 receptor. Ex vivo autoradiographic study in rats exhibited selective binding of (11)C-5-OH-DPAT to the striata. A PET study in a rhesus monkey showed selective localization of (11)C-5-OH-DPAT in the striata and the ratio between striata and cerebellum approached approximately 2 at 40 min postinjection.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Quantitation of striatal and extrastriatal D-2 dopamine receptors using PET imaging of [(18)F]fallypride in nonhuman primates.

[(18)F]Fallypride is a highly selective, high-affinity dopamine D-2 receptor ligand. The high affinity, K(D) = 30 pM, makes it a suitable candidate for visualizing both striatal and extrastriatal binding in the brain. In this work, dynamic PET studies of two macaque monkeys were acquired along with arterial plasma samples. Compartmental analysis and Logan plots were used to analyze the striatum, thalamus, frontal, and temporal cortices and to validate a reference region of analysis which yields a distribution volume ratio (DVR). The cerebellum was used as the reference region. The results indicate that all methods of analysis are in close agreement over all the analyzed regions in the brain. The average DVRs for the two monkeys was found to be: caudate = 26, putamen = 29, thalamus = 3.8, frontal ctx = 1.7, and temporal ctx = 1.7 on a high-resolution PET scanner. It was found that a scan time of 2 h is needed to accurately estimate the DVR for all regions of the brain. The striatal regions require the longest to linearize and are the most sensitive to variations in the average tissue-to-plasma efflux constant, k(2). For the extrastriatal regions, the effect of the k(2) term on DVR calculation is negligible. Repeatability measurements for all regions were found to be within 10% using the DVR parameter.

Animals↗
PubMed2006

Reliability of a method to measure novelty-seeking in nonhuman primates.

The objective of this study was to create a reliable method to measure novelty-seeking (NS) temperament in stumptailed macaques. We correlated two behavioral indexes (risk-taking and curiosity) with the NS index. Cochran's concordance index yielded ethogram reliability (risk: alpha = 0.88; curiosity: alpha = 0.79). Risk and curiosity indexes were obtained with a synthetic index obtainment approach. Intraclass correlation of the instrument yielded a value of 0.88. Temperament index was established from the average score given by each judge. The instrument presented 92% specificity and 70% sensitivity, with a 56-point score taken as the cuttoff point to classify individuals. The results of a Spearman's analysis of the three indexes were significant (temperament-risk, n = 32, P<0.01; temperament-curiosity, n = 29, P<0.05; risk curiosity, n = 29, P<0.05). We conclude that the method we developed is reliable.

Animals↗
PubMed2007

Which senses play a role in nonhuman primate food selection? A comparison between squirrel monkeys and spider monkeys.

In order to optimize foraging efficiency and avoid toxicosis, animals must be able to detect, discriminate, and learn about the predictive signals of potential food. Primates are typically regarded as animals that rely mainly on their highly developed visual systems, and little is known about the role that the other senses may play in food selection. It was therefore the aim of the present study to assess which senses are involved in the evaluation of food by two species of New World primates: the squirrel monkey and the spider monkey. To this end, six animals per species were repeatedly presented with both familiar and novel food items, and their behavior was videotaped and analyzed. To obtain a further indication of the relative importance of visual and chemosensory cues, the animals were also presented with familiar food items that were experimentally modified in color, odor, or both color and odor. The results demonstrate that squirrel monkeys and spider monkeys use olfactory, gustatory, and tactile cues in addition to visual information to evaluate novel food, whereas they mainly inspect familiar food items visually prior to consumption. Our findings also show that in both species the use of nonvisual cues decreased rapidly with repeated presentations of novel food, suggesting a fast multimodal learning process. Further, the two species clearly differ in their relative use of nonvisual cues when evaluating novel or modified food, with spider monkeys relying more on olfactory cues than squirrel monkeys, and squirrel monkeys relying more on tactile cues compared to spider monkeys.

Animals↗
PubMed2001

Nonhuman primate hybridization and the taxonomic status of Neanderthals.

The present study examines the taxonomic status of Middle Paleolithic Neanderthals by comparing their observed minimum genetic divergence from Upper Paleolithic modern humans in Europe with that observed between macaque species from Sulawesi that are known to hybridize and fully intergrade in the wild. The genetic divergence, and differentiation between Neanderthals and Upper Paleolithic modern humans, as indicated by pairwise minimum genetic distances and F(ST) values calculated from the estimated minimum genetic relationship (R) matrix derived from craniometric data, are significantly greater than those observed both between hybridizing and noninterbreeding Sulawesi macaque species, suggesting that mate recognition and the possibility of gene flow between Neanderthals and Upper Paleolithic modern humans might have been greatly reduced. These results support a species-level taxonomic distinction for the Neanderthals as suggested by proponents of the replacement model. Furthermore, assumptions regarding the monophyletic origin of modern humans from outside Europe are likely valid.

Animals↗
PubMed1993

Basicranial flexion, relative brain size, and facial kyphosis in nonhuman primates.

Numerous hypotheses explaining interspecific differences in the degree of basicranial flexion have been presented. Several authors have argued that an increase in relative brain size results in a spatial packing problem that is resolved by flexing the basicranium. Others attribute differences in the degree of basicranial flexion to different postural behaviors, suggesting that more orthograde animals require a ventrally flexed pre-sella basicranium in order to maintain the eyes in a correct forward-facing orientation. Less specific claims are made for a relationship between the degree of basicranial flexion and facial orientation. In order to evaluate these hypotheses, the degree of basicranial flexion (cranial base angle), palate orientation, and orbital axis orientation were measured from lateral radiographs of 68 primate species and combined with linear and volumetric measures as well as data on the size of the neocortex and telencephalon. Bivariate correlation and partial correlation analyses at several taxonomic levels revealed that, within haplorhines, the cranial base angle decreases with increasing neurocranial volume relative to basicranial length and is positively correlated with angles of facial kyphosis and orbital axis orientation. Strepsirhines show no significant correlations between the cranial base angle and any of the variables examined. It is argued that prior orbital approximation in the ancestral haplorhine integrated the medial orbital walls and pre-sella basicranium into a single structural network such that changes in the orientation of one necessarily affect the other. Gould's ("Ontogeny and Phylogeny." Cambridge: Belknap Press, 1977) hypothesis, that the highly flexed basicranium of Homo may be due to a combination of a large brain and a relatively short basicranium, is corroborated.

Animals↗
PubMed1977

Muscle spindles in nonhuman primate extrinsic auricular muscles.

Muscle spindles were sought in peri-auricular muscles of several primate species (rhesus monkey, woolly monkey, and baboon). Transverse sections cut at 10 mu and stained primarily by a silver impregnation technique were examined using light microscopy. Spindles were identified on the basis of standard criteria. Posterior and/or superior auricular muscles of each species were found to contain spindles. At least some muscles innervated by facial nerve have classical spindles as component structures.

Animals↗
PubMed2005

Comparative study of lectin reactivity in the vomeronasal organ of human and nonhuman primates.

The main and accessory olfactory systems of certain mammals (e.g., rodents, ungulates, and carnivores) have been investigated using lectin histochemistry to probe for sugar residues that may reflect physiological aspects of signal transduction or development. Morphologically, the vomeronasal organs (VNOs) of strepsirrhine primates (lemurs and lorises) are typical of functional VNOs in other mammals, whereas in humans and chimpanzees the VNOs appear vestigial. However, the human VNO is considered functional by some authors. To elucidate the cellular nature of the VNO in human and chimpanzees, a panel of six lectins (Con-A, ECL, PNA, RCA, s-WGA, and UEA-1) was applied to the VNO in eight species of primates, including humans and chimpanzees. The results indicated that there were few, if any, lectin-reactive cells in the human or chimpanzee VNO that resembled those seen in the vomeronasal neuroepithelium in other primates. The overall pattern of lectin reactivity in the human and chimpanzee VNO is unlike that seen in mammals with chemosensory VNOs, suggesting that the VNO of these hominoids does not function similarly to that of other primates.

Animals↗
PubMed1984

A circular waveguide irradiation system for nonhuman primates: design and dosimetry.

A 275-MHz exposure system, consisting of a circular waveguide irradiator and a transparent plastic animal cage, has been developed to accommodate rhesus monkeys weighing up to 15 kg. The vertically oriented waveguide is composed primarily of stainless steel and is fitted with an inner cage fabricated from a tubular section of acrylic plastic. Circularly polarized electromagnetic energy at 275 MHz, either pulsed or continuous wave (CW), can be propagated from the removable top section of the waveguide. The cage is designed to function as the monkey's permanent home. It is fitted with a lever-actuated behavioral performance device on which the monkey responds according to a predetermined schedule to obtain a daily food ration. The system can be adapted to provide for the collection of metabolic and physiologic data as well. Dosimetric measurements were conducted with six rhesus monkeys weighing 3.0-7.2 kg and with a 4-kg model. The dosimetric results show that about one-third of the net incident energy is absorbed by a subject in this system at a normalized specific absorption rate (SAR) of 0.33 (W/kg)/(mW/cm2).

Animals↗
PubMed1995

Initial exposure to 30 kV/m or 60 kV/m 60 Hz electric fields produces temporary cessation of operant behavior of nonhuman primates.

In two separate experiments, we examined the effects of a 60 Hz electric field (EF) on performance of an operant schedule consisting of two signaled components: fixed-ratio (FR30) and differential reinforcement of low-rate (DRL20). In each experiment, 12 naive baboons (Papio cynocephalus) were assigned randomly to either an EF-exposed experimental group or a sham-exposed control group. A homogeneous vertical EF of 30 kV/m was used in one experiment; 60 kV/m was used in the other. The experimental design for both experiments included 6 week preexposure, exposure, and postexposure periods. The planned analyses indicated no evidence of statistically significant (P < .05) effects of EF exposure. However, exploratory analyses comparing performance during the last week of preexposure and the first week of exposure revealed statistically significant acute effects (work stoppage): The mean response rates of the EF-exposed groups were greatly reduced on day 1 of exposure but were normal by the end of day 2 of EF exposure. We hypothesize that introduction of a highly unusual stimulus, the EF, temporarily interfered with normal operant behavior to produce a primary work stoppage. Supplementary cross-over experiments added at the end of each main experiment indicated that work stoppage occurred again when formerly EF-exposed subjects served as sham-exposed controls, while other subjects received their first EF exposure. Presumably, reoccurrence of other stimuli correlated with initial exposure to the EF became sufficient to subsequently cause secondary work stoppage in the absence of direct EF exposure. The primary and secondary work-stoppage effects were reproducible.

Animals↗
PubMed1995

Chronically indwelling venous cannula and automatic blood sampling system for use with nonhuman primates exposed to 60 Hz electric and magnetic fields.

An automated blood sampling system was developed for use with tethered baboons (Papio cynocephalus) during concurrent exposure to 60 Hz 30 kV/m electric fields and 0.1 mT (1.0 G) magnetic fields. The system was controlled by a FORTH-based microcomputer, which operated a pump, a fraction collector, and two pinch valves. A swivel mechanism at the end of the tether allowed the baboons to move freely in their cages. The hardware and software were designed for fail-safe operation. Heparinized saline was infused at a rate of 0.5 mL/min until a sample cycle was initiated. Then, blood was drawn from the animal into a storage tube at a rate of 12.5 mL/min, a sample of undiluted blood was taken from the end of the storage tube near the baboon, and the blood remaining in the storage tube was then flushed back into the animal. Use of the storage tube prevented the peristaltic pump rollers from pressing on tubing containing blood, and return of the blood diluted with saline limited the blood wasted per sample to less than 0.5 mL. The system functioned reliably in three experiments, collecting samples as scheduled 97% of the time. Although it was initially designed for and used successfully with primates in an electric and magnetic field environment, this type of system could be employed in many areas of biomedical research or medical treatment.

Animals↗