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Biomedical subjects

Carlos Tomaz

Publications and source records attributed to Carlos Tomaz.

At least 19 recordsLinked to original sources

Interaction of the tachykinin NK3 receptor agonist senktide with behavioral effects of cocaine in marmosets (Callithrix penicillata).

Brain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, antagonism of the tachykinin NK3-receptor (NK3-R), one of the three tachykinin receptors in the brain, was shown to attenuate the acute and chronic behavioral effects of cocaine in rats and the acute effects in non-human primates. In order to expand these findings we investigated the effects of the NK3-R agonist, succinyl-[Asp6, Me-Phe8]SP(6-11) (senktide), on the acute behavioral effects of cocaine in marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals were pretreated with senktide (0, 0.1, 0.2, 0.4 mg/kg, s.c.), and received either a treatment with cocaine (10 mg/kg) or saline (i.p.). Cocaine increased locomotor activity and the duration of aerial scanning behavior, but reduced exploratory activity, bodycare activity, the frequency of aerial scanning, and terrestrial glance behavior. Senktide blocked the effects of cocaine on locomotor activity, but enhanced the cocaine effects on exploratory activity, aerial scanning frequency, and terrestrial glance behavior. Senktide alone did not significantly influence monkey behavior in this study. These data expand previous findings suggesting a complex role of the NK3-R in the acute behavioral effects of cocaine in non-human primates.

Animals↗

The tachykinin NK3 receptor antagonist SR142801 blocks the behavioral effects of cocaine in marmoset monkeys.

Brain neuropeptide transmitters of the tachykinin family are involved in the organization of many behaviors. However, little is known about their contribution to the behavioral effects of drugs of abuse. Recently, the tachykinin NK3 receptor, one of the three tachykinin receptors in the brain, was shown to attenuate the acute and chronic behavioral effects of cocaine in rats. In order to test if these findings can be generalized to primates we investigated the role of the tachykinin NK3 receptor in the acute behavioral effects of cocaine in marmoset monkeys (Callithrix penicillata) using a figure-eight maze procedure. Animals were pretreated with the tachykinin NK3 receptor antagonist, (R)-(N)-[1-[3-[1-benzoyl-3-(3,4-dichlorophenyl)piperidin-3-yl]propyl]-4-phenylpiperidin-4-yl]-N-methylacetamide (SR142801; 0, 0.02, 0.2, 2.0 mg/kg, i.p.), and received either a treatment with cocaine (10 mg/kg, i.p) or saline (i.p.). Cocaine increased locomotor activity and aerial glance behavior, but reduced exploratory and bodycare activities, scent marking and terrestrial scanning behavior. A sensitivity analysis revealed that two responder types can be differentiated in relation to the occurrence of a hyperlocomotor response to cocaine. SR142801 blocked the actions of cocaine on several behaviors dose-dependently for each responder type, respectively. There was no effect of SR142801 alone on any behavior measured. These data suggest that the tachykinin NK3 receptor contributes to the individual behavioral response to cocaine in marmoset monkeys. Having no behavioral effects on its own, but blocking the cocaine effects, might suggest the tachykinin NK3 receptor antagonist, SR142801, as a potential treatment of cocaine addiction in humans.

Analysis of Variance↗

Sex-related lateralized effect of emotional content on declarative memory: an event related potential study.

Several studies suggest that emotional arousal can promote memory storage. In this study, we evaluated the effects of emotional content on declarative memory, utilizing an adaptation of two versions of the same story, with different arousing properties (neutral or emotional), which have been already employed in experiments involving the enhancing effects of emotions on memory retention. We used event related potentials (ERP) to evaluate whether there is a sex-related hemispheric lateralization of electrical potentials elicited by the emotional content of a story. We compared left and right hemisphere P300 waves, recorded in P3 and P4 electrode sites, in response to emotional or neutral stimuli in men and women. In the left hemisphere, emotional stimuli elicited a stronger P300 in women, compared to men, as indexed by both amplitude and latency measures; moreover, the emotional content of the story elicited a stronger P300 in the right hemisphere in men than in women. The better memory for the arousal material may be related to the differential P300 at encoding. These data indicate that both sex and cerebral hemisphere constitute important, interacting influences on neural correlates of emotion, and of emotionally influenced memory.

Adult↗

Serotonin1A-receptor antagonism blocks psychostimulant properties of diethylpropion in marmosets (Callithrix penicillata).

Diethylpropion (1-phenyl-2-diethylamine-1-propanone hydrochloride) is a stimulant drug with reinforcing properties that is used to treat obesity in humans. While the anorectic properties of diethylpropion are mediated by a noradrenergic mechanism, stimulant properties depend on its effects on the serotonergic (5-HT) and/or dopaminergic systems. In this study we investigated the role of the 5-HT1A-receptor in the acute behavioral effects of diethylpropion in marmosets (Callithrix penicillata). Animals were pretreated with the selective 5-HT1A-receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide trihydrochloride (WAY 100635; 0.2, 0.4, 0.8 mg/kg, i.p.) or saline (i.p.) and received a treatment with diethylpropion (10 mg/kg, i.p) or saline (i.p.). Diethylpropion induced an increase in locomotor activity in 60% of the monkeys, which were classified as diethylpropion sensitive, but did not affect locomotion in 40% of the monkeys (diethylpropion insensitive). Sensitivity analysis revealed two types of responders to diethylpropion. In the sensitive animals (type A) diethylpropion increased locomotor activity and anxiogenic-like behavior, but decreased bodycare activities. In the insensitive animals (type B) diethylpropion did not affect locomotor and bodycare activity after diethylpropion, but led to a strong increase in anxiogenic-like behavioral responses. Selective 5-HT1A-receptor antagonism modulated the acute diethylpropion effects responder type specifically. In the sensitive (type A) monkeys WAY 100635 blocked the diethylpropion-induced increase in locomotor activity, while not affecting anxiogenic-like behavioral responses or the suppression of bodycare activities. In the insensitive monkeys, WAY 100635 had no effect on locomotor activity after diethylpropion, but blocked diethylpropion effects on some anxiogenic-like behavioral responses. In conclusion, these results suggest an essential contribution of the 5-HT1A-receptor to the stimulant effects of diethylpropion, which is responder type specific. It also suggests the 5-HT1A-receptor to be a source of the interindividual variance in the acute behavioral response to the stimulant diethylpropion in monkeys.

Analysis of Variance↗

Influence of stimuli size on color discrimination in capuchin monkeys.

Large-field trichromacy is a general feature of protanope and deuteranope humans, provided that the stimuli size extends to an 8 degrees visual angle. In this study we compared the performance of five male and three female tufted capuchin monkeys (Cebus apella) in discriminating pairs of Munsell color papers. Human subjects were also studied in two-choice discrimination tests, using the same stimuli and apparatus employed for the monkeys. The results show that although the dichromatic humans showed improved discrimination with larger versions of the stimuli, the dichromatic monkeys exhibited the same performance for both stimuli sizes. Thus, Cebus apella apparently do not present large-field trichromacy-at least for the conditions in the present experiments.

Adult↗

Color vision in marmosets and tamarins: behavioral evidence.

Here we demonstrate differences in the relative performance of 15 callitrichids tested in a series of color visual discrimination experiments. Munsell color chips were chosen as stimuli based on their use in earlier experiments with human dichromats. We show behavioral evidence for the existence of four distinct kinds of color-vision phenotypes, each of which has slightly different color discrimination abilities. The different phenotypes may offer different advantages. The data are in accordance with the existence of a visual polymorphism in callitrichids.

Animals↗

Effect of iron-fortified drinking water of daycare facilities on the hemoglobin status of young children.

BACKGROUND: Anemia is the most prevalent nutrition problem in young children. One possible strategy to prevent anemia is affordable fortification of drinking water. OBJECTIVE: The aim of this study was to evaluate the impact of iron-fortified drinking water of daycare facilities on the hemoglobin and anthropometric status of pre-school children. DESIGN: Hemoglobin (Hb) status, weight and height measurements were assessed in 160 pre-school children aged 6 to 59 m before and after 8 m consumption of iron- (12 mg/L) and vitamin C- (90 mg/L) fortified drinking water. RESULTS: Initially, 43.2% (69) of the children evaluated as being anemic decreased to 21% (37) at the end of study. At baseline, 42 (26.3%) children suffered from moderate anemia and 27 (16.9%) suffered severe anemia, but after iron fortification, total number of children suffering from moderate and severe anemia had decreased to 32 (20.7%) and 5 (3%), respectively. Weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height (WHZ) Z-scores increased significantly from -0.84 +/- 1.03 to 0.06 +/- 1.10, -0.84 +/- 1.11 to 0.54 +/- 1.10 and -0.39 +/- 0.94 to -0.18 +/- 1.14, respectively (p < 0.05). Daycare personnel reported increased appetite and food consumption and decreased absenteeism during intervention. CONCLUSION: Daily consumption of iron-fortified drinking water in daycare facilities is an effective, simple and inexpensive means of reducing and controlling for moderate and severe anemia in pre-school children.

Anemia, Iron-Deficiency↗

Hippocampus 5-HT(1A)-receptors attenuate cocaine-induced hyperlocomotion and the increase in hippocampal but not nucleus accumbens 5-HT.

Cocaine induces an increase in hippocampal and nucleus accumbens (Nac) serotonin (5-HT) concentration parallel to locomotor activation. Both effects can be modulated by systemic 5-HT(1A)-receptor agonism/antagonism. Given the contribution of the hippocampus to spontaneous behavioral activity, these observations suggest a role for hippocampal 5-HT as well in the modulation of cocaine effects on behavior. To determine the role of hippocampal 5-HT(1A)-receptors in cocaine effects on behavior and hippocampal 5-HT release, we used in vivo microdialysis in freely moving rats. The 5-HT(1A)-receptor agonist, 8-OH-DPAT (0, 0.1, 1 and 10 microM), was applied locally into the hippocampus by reversed dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The hippocampal 5-HT(1A)-receptor activation attenuated cocaine-induced hyperlocomotion and rearing behavior dose-dependently. Parallel to that, the cocaine-induced 5-HT increase was attenuated dose-dependently in the hippocampus but was left unaffected in the Nac. The intra-hippocampal application of 8-OH-DPAT affected neither behavioral activity nor 5-HT concentration in the hippocampus and in the Nac. In accord with these findings, hippocampal 5-HT(1A)-receptors may not be directly involved in the regulation of spontaneous behavior or basal 5-HT concentration in the hippocampus and Nac. However, the results indicate an inhibitory role of hippocampal 5-HT(1A)-receptors in cocaine-induced hyperactivity and in the 5-HT increase evoked by cocaine in the hippocampus but not in the Nac.

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

Multibehavioral analysis of fear and anxiety before, during, and after experimentally induced predatory stress in Callithrix penicillata.

A detailed behavioral analysis of nine Callithrix penicillata was conducted in the Marmoset Predator Confrontation Test (MPCT) during (a) four habituation trials with no "predator," (b) six confrontation trials with the predator (taxidermized oncilla cat, Felis tigrina), and (c) four trials with the predator removed. The marmosets habituated to the test apparatus with significant decreases in locomotion, exploration and long calls. Initial exposure to the predator elicited mainly fear-related behaviors (proximic avoidance, tsik-tsik vocalization, swaying/tongue in-out), whereas repeated confrontations attenuated these behaviors, concomitant to an increase in anxiety-associated responses (scratching/grooming/scent marking). The initial behavioral repertoire, observed before confrontations, was fully restored only upon removal of the predator. This easily discernable complex defensive behavioral repertoire is hoped to provide a comprehensive baseline for studying the biological substrates of fear/anxiety parameters in nonhuman primates.

Animals↗

Anxiolytic-like effects of the selective 5-HT1A receptor antagonist WAY 100635 in non-human primates.

Non-human primates provide important insights into the potential use of 5-HT(1A) receptor antagonists in treating human anxiety disorders and as research tools, given the existent inconsistencies in rodent tests. This study investigated the effects of the selective silent 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexane-carboxamide trihydrochloride (WAY 100635), administered systemically, in an ethologically based fear/anxiety test in marmoset monkeys (Callithrix penicillata). Subjects were tested using a figure-eight maze and a taxidermized wild cat as 'predator' stimulus. After seven 30-min maze habituations in the absence of the 'predator', each animal was submitted to four pseudo-randomly assigned 30-min treatment trials in the presence of the 'predator': three WAY 100635 (0.2, 0.4 and 0.8 mg/kg, i.p.) sessions and a saline control trial. The 'predator' stimulus caused a significant fear-induced avoidance of the maze sections closest to where it was presented, indicating an anxiogenic effect. However, WAY 100635 treatment reversed, significantly and dose-dependently, this fear-induced avoidance behavior, while increasing maze exploration. Sedation was not observed. This is the first study to suggest an anxiolytic-like effect of the selective silent 5-HT(1A) receptor antagonist WAY 100635 in non-human primates, indicating its potential use as a therapeutic agent.

Animals↗

Colour discrimination learning in black-handed tamarin ( Saguinus midas niger).

Colour is one cue that monkeys use for perceptual segregation of targets and to identify food resources. For fruit-eating primates such as Saguinus, an accurate colour perception would be advantageous to help find ripe fruits at distance. The colour vision abilities of black-handed tamarins ( Saguinus midas niger) were assessed through a discrimination learning paradigm using Munsell colour chips as stimuli. Pairs of chips were chosen from an early experiment with protan and deutan humans. The monkeys (three males and one female) were tested with stimuli of the same hue, but different brightness values, in order to make sure that discriminations were based on colour rather than brightness cues. The results showed that the female, but not the males, presented an above-chance performance for stimuli resembling hue conditions under which tamarins forage (oranges vs greens). Colour vision in S. m. niger is discussed according to the advantages and disadvantages of dichromatism in daily search for food as well as to aspects regarding polymorphism in New World monkeys.

Animals↗

Lateralized impairment of the emotional enhancement of verbal memory in patients with amygdala-hippocampus lesion.

This study investigated amygdala-hippocampus's functional asymmetry in the emotional modulation of memory for stories. Thirty-nine, right-handed, drug-resistant epilepsy patients who had been submitted to unilateral temporal lobectomy (19 left and 20 right) watched either an arousing or neutral version of a story presented audio-visually. The slide sequence was the same in the neutral and arousing version, the narratives were matched for structure and comprehensibility. The set and order of the 11 slide sequence were identical in both conditions. Free recall and recognition measures were taken 2h after story presentation. Subjects in the TLE group who watched the arousing version recalled more details than the subjects who watched the neutral version (t(37)=3.4,p<.001). The group who watched the arousing version recalled more details of the phase 2 of the story (t(37)=6.76,p<.001). Scores in both conditions did not differ between control subjects and temporal lobectomy patients. When the right and left lesioned groups' results were analyzed separately, it was observed that the two groups did not differ in their recall of the neutral version. The right lesioned group recalled more items of the arousal than the neutral version (Z=-3.55,p<.001). However the left lesioned group did not show the memory enhancement for the emotional version, in this group it was only found an enhanced recall of the more pictorial emotional segment of the narrative (Z=-3.11,p<.001). This illustrates that the right amygdala can influence retention of complex emotional stimuli with verbal and pictorial arousing properties. We concluded that an intact left amygdala-hippocampus is important for enhancement of memory related to emotionally arousing verbal material.

Acoustic Stimulation↗

Ontogenetic dissociation between habit learning and recognition memory in capuchin monkeys (Cebus apella).

The performance of young and adult capuchin monkeys (Cebus apella) on a Concurrent Discrimination Learning (CDL) test and a Delayed Non-Matching to Sample (DNMS) task were investigated. Results indicate that all subjects were able to learn the CDL test with 20-pairs simultaneously and retain this stimulus/reward association within 24-h interval. In contrast, young subjects did not perform the DNMS task with the same proficiency as adults. While adults' scores were above chance across all memory test delays, the young capuchin monkeys performed the test by chance level. These results support the hypothesis that these two tasks require different cognitive processes mediated by two independent neural systems with a differentiated ontogenetic development. Moreover, they provide evidence that this dissociation occurs not only in humans and Old World monkeys but also in the New World capuchin monkeys indicating that this species can be a valuable alternative model for investigations of the neurobiological basis of memory.

Age Factors↗

The selective serotonin(1A)-receptor antagonist WAY 100635 blocks behavioral stimulating effects of cocaine but not ventral striatal dopamine increase.

An increase in the extracellular dopamine (DA) concentration is generally accepted as an important neurochemical mediator of the behavioral effects of cocaine. Cocaine induced increases in serotonergic (5-HT) activity also appears to be involved in these effects. Here we describe the effects of the 5-HT(1A)-receptor antagonist WAY 100635 on the behavioral and neurochemical effects of cocaine. In-vivo microdialysis was used in behaving rats to measure extracellular concentration of DA in the nucleus accumbens (Nac). Four groups of animals received one of the following drug combinations: WAY 100635 (0.4 mg/kg) and cocaine (10 mg/kg), saline and cocaine (10 mg/kg), WAY 100635 (0.4 mg/kg) and saline, or saline and saline. The injections were administered i.p. and spaced 20 min apart. The pretreatment with WAY 100635 significantly attenuated the locomotor stimulant effects of cocaine without altering the DA overflow in the Nac. WAY 100635 itself did not modify locomotion or the extracellular DA concentration in the Nac. These results indicate that (1) the 5-HT(1A)-receptor is an important component in the mediation of cocaine locomotor stimulant effects, and (2) an increase in the extracellular DA concentration in the Nac might be a necessary but is not a sufficient condition for the locomotor stimulant effects of cocaine.

3,4-Dihydroxyphenylacetic Acid↗

Working memory in capuchin monkeys (Cebus apella).

It has been suggested that delayed (non-) matching to sample (DNMTS/DMTS) tasks using trial-unique stimuli and short, as well as longer delay intervals, can provide important insights into animal cognition. Therefore, this research examined the capability of the New World capuchin monkey (Cebus apella) in perform trial-unique DMTS and DNMTS tasks across delay intervals ranging between 8 s and 10 min. Subjects were tested using a version of the Wisconsin General Test Apparatus mounted in front of the animal's home cage. They were first trained on a basic DMTS/DNMTS task with an 8 s interval until they reached a learning criterion of nine correct responses in ten consecutive trials. All subjects reached the learning criterion in both DMTS/DNMTS tasks, and the number of trials to criterion did not differ between tasks. After reaching the criterion, subject's memory performance was successively assessed at delay intervals of 15 s, 60 s, 120 s and 10 min. For both DMTS/DNMTS tasks, the mean percentage of correct responses across delays was above chance and, interestingly, performance did not significantly decrease as function of delay increments. Comparisons based on each group's scores, averaged across the four delays, showed no difference between DMTS and DNMTS memory performance. These results indicate that capuchin monkeys are able to learn DMTS/DNMTS tasks in which they are required to respond to new pairs of stimuli on every trial. This demonstrates the capability of 'concept' learning in this species. Moreover, above chance performance on the memory tests indicates a working memory ability similar to that reported for the genus Macaca. Taken together, these data indicates that capuchin monkeys can be a valuable alternative model for investigations of the neuropsychological basis of memory.

Animals↗

Color vision perception in the capuchin monkey (Cebus apella): a re-evaluation of procedures using Munsell papers.

In previous experiments based on color vision discrimination of Munsell chips, Pessoa et al. (Behav Brain Res 1997;89:285-8) presented evidence of trichromatic color vision in capuchin monkeys. However, the possibility of subjects using brightness cues was not eliminated. The purpose of the present study was to reassess the color perception in Cebus apella in a similar behavioral paradigm, but using a range of brightness values at each tested hue. We now report that male capuchins show a dichromatic behavior. The results are discussed in terms of the hypothesis of male dichromatism in the New World monkey, the biological role of color vision and cognitive abilities of capuchin monkeys.

Adult↗

Non-human primate models for investigating fear and anxiety.

Non-human primates exhibit similar physiological and behavioral responses to anxiety-inducing situations as humans and have, in fact, been successfully employed in both conditioned (i.e. conflict paradigms) and ethologically based tests of fear/anxiety (i.e. involuntary isolation, social interaction, human threat, predator confrontation). In the last decade, a renewed and growing interest in non-human primate models has resulted from the use of the small callitrichid species in behavioral pharmacology and neuroscience. This review focuses on the available non-human primate models for investigating fear/anxiety, addressing their advantages, shortcomings, and conceptual framework on which they are based. Lastly, a new ethologically based model to study anxiety and fear-induced avoidance in callitrichids--the marmoset predator confrontation test--is discussed.

Animals↗

Anxiolytic-like effects of substance P fragment (SP(1-7)) in non-human primates (Callithrix penicillata).

The behavioral effects of the amino (N)-terminal fragment of substance P (SP(1-7)) on the marmoset (Callithrix penicillata) predator confrontation test of fear/anxiety were investigated. The test apparatus consisted of a figure-eight maze with three parallel arms interconnected at each extremity to a perpendicular arm. A taxidermized oncilla cat (Felis tigrina) was placed outside the maze facing one of its corners. Subjects were submitted to seven 30 min maze habituation trials (HTs), in the absence of the 'predator', and then to six 30 min treatment trials (TTs), in the presence of the 'predator', consisting of four doses of SP(1-7) (5, 50, 250 and 500 microg/kg; IP), saline and sham injection. SP(1-7) treatment reversed, in a dose-dependent way, the fear-induced avoidance behavior due to the predator's presence and increased the frequency of exploratory behaviors. Locomotor activity decreased during successive HTs, yet increased after all SP(1-7) treatments. These results indicate that systemic administration of SP(1-7) produces anxiolytic-like effects in marmosets tested in the predator confrontation model of fear/anxiety.

Animals↗