Mecanismos de sincronia social no ritmo circadiano de atividade durante a coabitação em casais de saguis (Callithrix jacchus)

In marmosets, it was observed that the synchrony among circadian activity profiles of animals that cohabite in family groups is stronger than those of the same sex and age of different families. Inside the group, it is stronger between the younger ones than between them and their parents. However, the mechanisms involved in the social synchrony are unknown. With the aim to investigate the synchronization mechanisms involved in the synchrony between the circadian activity profiles during cohabitation in pairs of marmosets, the motor activity was continuously registered by the use of actmeters on three dyads. The pairs were maintained in two different conditions of illumination: light-dark cycle LD 12:12 (LD cohabitation I – 21 days), and thereafter in LL (~350 lux). Under LL, the pairs were submitted to four experimental situations: 1. Cohabitation (LLJ I – 24 days), 2. Removal of one member of the pair to another room with similar conditions (LLS I – 20 days), 3. Reintroduction of the separated member in the cage of the first situation (LLJ II – 30 days) and 4. Removal of a member from each pair to another experimental room (LLS II – 7 days), to evaluate the mechanisms of synchronization. Ultimately, the members of each pair were reintroduced in the cage and were kept in LD cycle 12:12 (LDJ II – 11 days). The rhythms of pairs free-ran in LL, with identical periods between the members of each pair during the two stages of cohabitation. In the stages in which the animals were separated, only the rhythms of two females free-ran in the first stage and of three animals in the second one. In those conditions, the rhythms of animals of each pair showed different endogenous periods. Besides, during cohabitation in LD and LL, the members of each pair showed a stable phase relationship in the beginning of the active phase, while in the stages in which the animals were separated it was noticed a breaking in the stability in the phase relationships between the circadian activity profiles, with an increase in the difference in the phase angles between them. During cohabitation, at the transition between LD and LL, all animals showed free-running rhythms anticipating progressively the beginning and the end of the active phase in a phase similar to the previous condition, showing signs of entrainment to the previous LD. While in the posterior stages this was observed in only three animals between: LLT I and LLS I, and LLT II and LLS II, evidencing signs of entrainment to social cues between the members of each pair. On the other hand, one animal delayed progressively between LLT I and LLS I, three animals delayed between LLS I and LLT II, and three animals between LLT II and LLS II, perhaps by entrainment to the animals maintained outdoors in the colony. Similar process was observed in four animals between LLS II and LDT II, indicating entrainment to LD. In the transition between LLS I and LLT II, signs of masking was observed in the rhythm of a female in response to the male and in another pair in the rhythm of the male in regard to that of the female. The general and maximum correlations in the circadian activity profiles were stronger during cohabitation in LD and LL than in the absence of social contact in LL, evidencing the social effect. The cohabiting pairs had higher values of the maximum correlation in LD and LL than when the profiles were correlated to animals of different cages, with same or different sexes. Similar results were observed in the general correlation. Therefore, it is suggested that cohabitation induces a strong synchrony between circadian activity profiles in marmosets, which involves entrainment and masking. Nevertheless, additional studies are necessary to evaluate the effect of social cues on the synchronization of the circadian rhythm in pairs of marmosets in the absence of external social cues in order to confirm this hypothesis.

Modulaçao do estresse social sobre parâmetros fisiológicos, comportamentais, cognitivos e plasticidade neuronal em saguis (Callithrix jacchus) juvenis: um modelo psiquiátrico e cognitivo

Nos períodos críticos de plasticidade neural ocorre uma maior permissividade do sistema nervoso ao ambiente, por isto, a ação do estresse sobre o individuo e suas repercussões sobre áreas responsáveis pelo controle dos sistemas de resposta ao estresse e por funções cognitivas complexas vem recebendo bastante atenção. A utilização de modelos experimentais translacionais tem sido imprescindível na elucidação destes mecanismos e das patologias associadas. Diante disto, este trabalho investigou os efeitos do estresse social sobre parâmetros fisiológicos, comportamentais, cognitivos e sobre a neurogênese no córtex pré-frontal (CPF) durante um período crítico de plasticidade cerebral, a fase juvenil, em machos de Callithrix jacchus. Durante cinco meses, 5 animais foram acompanhados em suas famílias (GF) e 5 animais foram isolados socialmente por 4 meses (GI), após um mês em observação em ambiente familiar (fase basal- FB). Ao final do 5º mês foram aplicados 2 testes de memória de trabalho (MT) nos animais GF e GI. Em seguida, 3 animais de cada grupo foram sacrificados para análise do fator de neurogênese BDNF ( Brain Derived Neurotrophic Factor) por imunofluorescência no CPF (sub-regiões orbitofrontal e lateral). Os animais do GF não variaram significativamente o cortisol ao longo do estudo, enquanto o GI elevou o cortisol e comportamentos indicadores de ansiedade (CA) na primeira semana do isolamento. Em seguida, o GI apresentou uma redução no cortisol, nos CA, no peso corporal e um aumento de comportamentos estereotipados e da anedonia, alterações tipicamente depressivas em primatas não-humanos. Ao final, o GI apresentaram níveis de cortisol menores que em FB. Ambos os grupos apresentaram dificuldades em realizar e aprender as tarefas cognitivas e a presença de BDNF no córtex pré-frontal foi independente do grupo (GF ou GI), porém correlacionou-se com os níveis de cortisol presentes na ultima semana do estudo, e os animais com presença de BDNF no CPF lateral e orbitofrontal apresentaram maiores níveis de cortisol. Estes resultados contribuem no processo de validação do sagui como um bom modelo psiquiátrico translacional e aponta para possibilidade de estudos sobre transtornos depressivos na juventude e suas repercussões posteriores. Além disto, os resultados observados para as tarefas cognitivas levou-nos a fazer uma releitura dos protocolos utilizados em estudos de memoria de trabalho com animais adultos desta espécie, com a finalidade de aprimora-los facilitando a aprendizagem em animais juvenis, naives e em situações de estresse. Ademais, evidenciou-se pela primeira vez a relação do estresse, cortisol e níveis de BDNF, em animais juvenis desta espécie, com a fim de contribuir com sua utilização como modelo animal neurocognitivo.

Ansiedade social e cooperação em contexto de hierarquia social

The Ultimatum Game is a methodology of the Game Theory that intends to investigate the individuals cooperative behavior in situations of resources division. Studies have shown that half of the subjects don’t accept unfair division of resources, and prefer to bear a momentary cost to revenge the deceivers. However, people who have assertiveness impairment, such as social phobic individuals, could have some difficulties to reject unfair offer division resource, especially in situations that cause over anxiety, like being in the presence of an individual considered to be in a high hierarchical level. A negative perception about his own worth can also make the person thinks that he does not deserve a fair division. These individuals also have a strong desire to convey a positive impression to the others, which could cause them to be more generous in a resource division. The aim of this study was to verify, through the Ultimatum Game, if social anxiety individuals would accept more high confederate’s unfair offers that low confederate’s unfair offers; and if they would be more generous in goods division, in the same game, when compared to individuals without social anxiety. Ninety-five (95) college students participated in this study answering the Social Phobia Inventory, the Factorial Scale of Extroversion, socio-demographic questionnaire, situational anxiety scale and, finally, the Ultimatum Game in four rounds (1st and 3rd – confederate representing high or low ranking using an unfair proposal; 2nd – confederate without social status using fair proposal; 4th – subject’s research proposes the offer). The results showed a significant negative correlation between social anxiety and haughtiness, and social anxiety and assertiveness, and a significant positive correlation between social anxiety and situational anxiety. There was no significant difference in situational anxiety due to the status for anxious individuals. Also we found no significant difference in the amount of donated goods, showing that generous behavior does not differ between groups. Finally, the social status did not influence the decision in response to the game for anxious individuals. These results corroborate to other studies that show the relationship between social anxiety and assertiveness, and social anxiety and negative self-perception capability and value (low haughtiness). As show the results of situational anxiety scale, the high status stimulus was not perceived as threatening to the individual, which may have affected his answer in the game. The results for the Ultimatum Game follow the same direction as the acceptance rate for unfair proposals (approximately 50%) in studies with non-clinical sample.

Behavioural profiles of captive capuchin monkeys (Sapajus spp.): analyses at group and individual levels

The use of behavioural indicators of suffering and welfare in captive animals has produced ambiguous results. In comparisons between groups, those in worse condition tend to exhibit increased overall rate of Behaviours Potentially Indicative of Stress (BPIS), but when comparing within groups, individuals differ in their stress coping strategies. This dissertation presents analyses to unravel the Behavioural Profile of a sample of 26 captive capuchin monkeys, of three different species (Sapajus libidinosus, S. flavius and S. xanthosternos), kept in different enclosure types. In total, 147,17 hours of data were collected. We explored four type of analysis: Activity Budgets, Diversity indexes, Markov chains and Sequence analyses, and Social Network Analyses, resulting in nine indexes of behavioural occurrence and organization. In chapter One we explore group differences. Results support predictions of minor sex and species differences and major differences in behavioural profile due to enclosure type: i. individuals in less enriched enclosures exhibited a more diverse BPIS repertoire and a decreased probability of a sequence with six Genus Normative Behaviour; ii. number of most probable behavioural transitions including at least one BPIS was higher in less enriched enclosures; iii. proeminence indexes indicate that BPIS function as dead ends of behavioural sequences, and proeminence of three BPIS (pacing, self-direct, active I) were higher in less enriched enclosures. Overall, these data are not supportive of BPIS as a repetitive pattern, with a mantra-like calming effect. Rather, the picture that emerges is more supportive of BPIS as activities that disrupt organization of behaviours, introducing “noise” that compromises optimal activity budget. In chapter Two we explored individual differences in stress coping strategies. We classified individuals along six axes of exploratory behaviour. These were only weakly correlated indicating low correlation among behavioural indicators of syndromes. Nevertheless, the results are suggestive of two broad stress coping strategies, similar to the bold/proactive and shy/reactive pattern: more exploratory capuchin monkeys exhibited increased values of proeminence in Pacing, aberrant sexual display and Active 1 BPIS, while less active animals exhibited increased probability in significant sequences involving at least one BPIS, and increased prominence in own stereotypy. Capuchin monkeys are known for their cognitive capacities and behavioural flexibility, therefore, the search for a consistent set of behavioural indictors of welfare and individual differences requires further studies and larger data sets. With this work we aim contributing to design scientifically grounded and statistically correct protocols for collection of behavioural data that permits comparability of results and meta-analyses, from whatever theoretical perspective interpretation it may receive.

Ansiedade social e cooperação em contexto de hierarquia social

The Ultimatum Game is a methodology of the Game Theory that intends to investigate the individuals cooperative behavior in situations of resources division. Studies have shown that half of the subjects don’t accept unfair division of resources, and prefer to bear a momentary cost to revenge the deceivers. However, people who have assertiveness impairment, such as social phobic individuals, could have some difficulties to reject unfair offer division resource, especially in situations that cause over anxiety, like being in the presence of an individual considered to be in a high hierarchical level. A negative perception about his own worth can also make the person thinks that he does not deserve a fair division. These individuals also have a strong desire to convey a positive impression to the others, which could cause them to be more generous in a resource division. The aim of this study was to verify, through the Ultimatum Game, if social anxiety individuals would accept more high confederate’s unfair offers that low confederate’s unfair offers; and if they would be more generous in goods division, in the same game, when compared to individuals without social anxiety. Ninety-five (95) college students participated in this study answering the Social Phobia Inventory, the Factorial Scale of Extroversion, socio-demographic questionnaire, situational anxiety scale and, finally, the Ultimatum Game in four rounds (1st and 3rd – confederate representing high or low ranking using an unfair proposal; 2nd – confederate without social status using fair proposal; 4th – subject’s research proposes the offer). The results showed a significant negative correlation between social anxiety and haughtiness, and social anxiety and assertiveness, and a significant positive correlation between social anxiety and situational anxiety. There was no significant difference in situational anxiety due to the status for anxious individuals. Also we found no significant difference in the amount of donated goods, showing that generous behavior does not differ between groups. Finally, the social status did not influence the decision in response to the game for anxious individuals. These results corroborate to other studies that show the relationship between social anxiety and assertiveness, and social anxiety and negative self-perception capability and value (low haughtiness). As show the results of situational anxiety scale, the high status stimulus was not perceived as threatening to the individual, which may have affected his answer in the game. The results for the Ultimatum Game follow the same direction as the acceptance rate for unfair proposals (approximately 50%) in studies with non-clinical sample.

Caracterização do ritmo circadiano de atividade e repouso em saguis idosos (Callithrix Jacchus)

Advanced age may become a limiting factor for the maintenance of rhythms in organisms, reducing the capacity of generation and synchronization of biological rhythms. In this study, the influence of aging on the expression of endogenous periodicity and synchronization (photic and social) of the circadian activity rhythm (CAR) was evaluated in a diurnal primate, the marmoset (Callithrix jacchus). This study had two approaches: one with longitudinal design, performed with a male marmoset in two different phases: adult (three years) and older (9 y.o.) (study 1) and the second, a transversal approach, with 6 old (♂: 9.7 ± 2.0 y.o.) and 11 adults animals (♂: 4.2 ± 0.8 y.o.) (study 2). The evaluation of the photic synchronization involved two conditions in LD (natural and artificial illuminations). In study 1, the animal was subjected to the following stages: LD (12:12 ~ 350: ~ 2 lx), LL (~ 350 lx) and LD resynchronization. In the second study, the animals were initially evaluated in natural LD, and then the same sequence stages of study 1. During the LL stage in study 2, the vocalizations of conspecifics kept in natural LD on the outside of the colony were considered temporal cue to the social synchronization. The record of the activity was performed automatically at intervals of five minutes through infrared sensor and actimeters, in studies 1 and 2, respectively. In general, the aged showed a more fragmented activity pattern (> IV < H and > PSD, ANOVA, p < 0.05), lower levels of activity (ANOVA, p < 0.05) and shorter duration of active phase (ANOVA, p < 0.05) in LD conditions, when compared to adults. In natural LD, the aged presented phase delay pronounced for onset and offset of active phase (ANOVA, p < 0.05), while the adults had the active phase more adjusted to light phase. Under artificial LD, there was phase advance and greater adjustment of onset and offset of activity in relation to the LD in the aged (ANOVA, p < 0.05). In LL, there was a positive correlation between age and the endogenous period () in the first 20 days (Spearman correlation, p < 0.05), with prolonged  held in two aged animals. In this condition, most adults showed free-running period of the circadian activity rhythm with  < 24 h for the first 30 days and later on relative coordination mediated by auditory cues. In study 2, the cross-correlation analysis between the activity profiles of the animals in LL with control animals kept under natural LD, found that there was less social synchronization in the aged. With the resubmission to the LD, the resynchronization rate was slower in the aged (t-test; p < 0.05) and in just one aged animal there was a loss of resynchronization capability. According to the data set, it is suggested that the aging in marmosets may be related to: 1) lower amplitude and greater fragmentation of the activity, accompanied to phase delay with extension of period, caused by changes in a photic input, in the generation and behavioral expression of the CAR; 2) lower capacity of the circadian activity rhythm to photic synchronization, that can become more robust in artificial lighting conditions, possibly due to the higher light intensities at the beginning of the active phase due to the abrupt transitions between the light and dark phases; and 3) smaller capacity of non-photic synchronization for auditory cues from conspecifics, possibly due to reducing sensory inputs and responsiveness of the circadian oscillators to auditory cues, what can make the aged marmoset most vulnerable, as these social cues may act as an important supporting factor for the photic synchronization.

Caracterização do ritmo circadiano de atividade e repouso em saguis idosos (Callithrix Jacchus)

Advanced age may become a limiting factor for the maintenance of rhythms in organisms, reducing the capacity of generation and synchronization of biological rhythms. In this study, the influence of aging on the expression of endogenous periodicity and synchronization (photic and social) of the circadian activity rhythm (CAR) was evaluated in a diurnal primate, the marmoset (Callithrix jacchus). This study had two approaches: one with longitudinal design, performed with a male marmoset in two different phases: adult (three years) and older (9 y.o.) (study 1) and the second, a transversal approach, with 6 old (♂: 9.7 ± 2.0 y.o.) and 11 adults animals (♂: 4.2 ± 0.8 y.o.) (study 2). The evaluation of the photic synchronization involved two conditions in LD (natural and artificial illuminations). In study 1, the animal was subjected to the following stages: LD (12:12 ~ 350: ~ 2 lx), LL (~ 350 lx) and LD resynchronization. In the second study, the animals were initially evaluated in natural LD, and then the same sequence stages of study 1. During the LL stage in study 2, the vocalizations of conspecifics kept in natural LD on the outside of the colony were considered temporal cue to the social synchronization. The record of the activity was performed automatically at intervals of five minutes through infrared sensor and actimeters, in studies 1 and 2, respectively. In general, the aged showed a more fragmented activity pattern (> IV < H and > PSD, ANOVA, p < 0.05), lower levels of activity (ANOVA, p < 0.05) and shorter duration of active phase (ANOVA, p < 0.05) in LD conditions, when compared to adults. In natural LD, the aged presented phase delay pronounced for onset and offset of active phase (ANOVA, p < 0.05), while the adults had the active phase more adjusted to light phase. Under artificial LD, there was phase advance and greater adjustment of onset and offset of activity in relation to the LD in the aged (ANOVA, p < 0.05). In LL, there was a positive correlation between age and the endogenous period () in the first 20 days (Spearman correlation, p < 0.05), with prolonged  held in two aged animals. In this condition, most adults showed free-running period of the circadian activity rhythm with  < 24 h for the first 30 days and later on relative coordination mediated by auditory cues. In study 2, the cross-correlation analysis between the activity profiles of the animals in LL with control animals kept under natural LD, found that there was less social synchronization in the aged. With the resubmission to the LD, the resynchronization rate was slower in the aged (t-test; p < 0.05) and in just one aged animal there was a loss of resynchronization capability. According to the data set, it is suggested that the aging in marmosets may be related to: 1) lower amplitude and greater fragmentation of the activity, accompanied to phase delay with extension of period, caused by changes in a photic input, in the generation and behavioral expression of the CAR; 2) lower capacity of the circadian activity rhythm to photic synchronization, that can become more robust in artificial lighting conditions, possibly due to the higher light intensities at the beginning of the active phase due to the abrupt transitions between the light and dark phases; and 3) smaller capacity of non-photic synchronization for auditory cues from conspecifics, possibly due to reducing sensory inputs and responsiveness of the circadian oscillators to auditory cues, what can make the aged marmoset most vulnerable, as these social cues may act as an important supporting factor for the photic synchronization.

Preferência e competição alimentar em um grupo de Sapajus flavius em fragmento de Mata Atlântica em Caaporã – Paraíba – Brasil

Feeding is the primary selective pressure in all forms of animals. Nutritional ecological models predict consequences of preferred and non-preferred food consumption on behavioural, physiological and morphological adaptations. At same time, socioecological models infer socio-organizarion patterns based on feeding competition faced by animals. A list of preferred foods, and inferences regarding the intensity of feeding competition and its behavioural consequences are information of much importance for management of populations in fragments. In this work we observed the feeding behavior and spatial positioning of a group of more than 100 blond capuchin monkeys (Sapajus flavius) that inhabit a fragment of Atlantic forest, surrounded by sugarcane plantation. We compared the consumption of different food items with their monthly availability in the area to define the preferred and fallback food items. We recorded the vocalizations of aggression and the inter-individual distance (area of Minimum Convex Polygon/n individuals) to infer the type of food competition experienced by animals. In the year studied the fruit feeding time correlated with top consumed fruit productivity, indicating preference for fruits. Our data indicate that the species Elaeis sp., Cecropia palmata, Inga spp. and Simarouba amara are the preferred food items in the diet. Available all year round and uniformly distributed, sugarcane was a regular item in the diet and its was characterized as a staple fallback food for this group. Although fruits are preferential food items, direct competition rate did not correlate to fruit productivity in the area, maintaining the high rates throughout the year (2.45 events/ hour). The inter-individual distance index positively correlated with rain fall indicating scramble food competition. The number of neighbours of females carrying infants was smaller when fruit productivity is low, indicating that females carrying infants are suffering increased indirect competition. Our data indicates that blond capuchins in this fragment make use of sugar cane as a staple fallback food, which evidence the importance of sugar cane landscape for the survival of this critically endangered capuchin species in fragmented habitats in Northeast Brazil. A preliminary list of preferred and important foods is offered, and can assist in the choice of trees for reforestation, better fragments to be preserved and areas of release and translocation of animals. We did not observe an increase of contest competition while using preferred foods, but when using staple FBF. This may be due the altered environment, which results in high competition food throughout the year. Both the food preference as the social and behavioral consequences of high food competition experienced by animals in this fragment must be accompanied over the years to ensure the survival of this population.

Preferência e competição alimentar em um grupo de Sapajus flavius em fragmento de Mata Atlântica em Caaporã – Paraíba – Brasil

Feeding is the primary selective pressure in all forms of animals. Nutritional ecological models predict consequences of preferred and non-preferred food consumption on behavioural, physiological and morphological adaptations. At same time, socioecological models infer socio-organizarion patterns based on feeding competition faced by animals. A list of preferred foods, and inferences regarding the intensity of feeding competition and its behavioural consequences are information of much importance for management of populations in fragments. In this work we observed the feeding behavior and spatial positioning of a group of more than 100 blond capuchin monkeys (Sapajus flavius) that inhabit a fragment of Atlantic forest, surrounded by sugarcane plantation. We compared the consumption of different food items with their monthly availability in the area to define the preferred and fallback food items. We recorded the vocalizations of aggression and the inter-individual distance (area of Minimum Convex Polygon/n individuals) to infer the type of food competition experienced by animals. In the year studied the fruit feeding time correlated with top consumed fruit productivity, indicating preference for fruits. Our data indicate that the species Elaeis sp., Cecropia palmata, Inga spp. and Simarouba amara are the preferred food items in the diet. Available all year round and uniformly distributed, sugarcane was a regular item in the diet and its was characterized as a staple fallback food for this group. Although fruits are preferential food items, direct competition rate did not correlate to fruit productivity in the area, maintaining the high rates throughout the year (2.45 events/ hour). The inter-individual distance index positively correlated with rain fall indicating scramble food competition. The number of neighbours of females carrying infants was smaller when fruit productivity is low, indicating that females carrying infants are suffering increased indirect competition. Our data indicates that blond capuchins in this fragment make use of sugar cane as a staple fallback food, which evidence the importance of sugar cane landscape for the survival of this critically endangered capuchin species in fragmented habitats in Northeast Brazil. A preliminary list of preferred and important foods is offered, and can assist in the choice of trees for reforestation, better fragments to be preserved and areas of release and translocation of animals. We did not observe an increase of contest competition while using preferred foods, but when using staple FBF. This may be due the altered environment, which results in high competition food throughout the year. Both the food preference as the social and behavioral consequences of high food competition experienced by animals in this fragment must be accompanied over the years to ensure the survival of this population.

Efeitos in vivo e in vitro de agonistas parciais do receptor NOP: implicações para o tratamento da ansiedade, depressão e mania

Introduction: This study aimed to investigate the effects of the two peptide NOP partial agonists (UFP-113 and [F/G]N/OFQ(1-13)NH2) and the non peptide NOP partial agonist (AT-090) in the mouse emotional behavior as well as in the intracellular transduction pathways following the receptor binding. Methods: Male Swiss or CD-1 mice were used in this study together with NOP(+/+) and NOP(-/-) mice. The elevated plus maze (EPM) was used to evaluate the effects of compounds on anxiety-like behaviors. Diazepam and the NOP agonists, N/OFQ and Ro 65-6570, were used as positive controls in the EPM. NOP(+/+) and NOP(-/-) mice were used to evaluate the selectivity of those compounds that induced anxiolytic-like behaviors. The forced swim test (FST) was used to evaluate the effects of compounds on depressive-like behaviors. Nortriptyline and the NOP antagonists, UFP-101 and SB-612111, were used as positive controls in the FST. The effects of N/OFQ, UFP-101, SB-612111, UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090 were assessed in the methylphenidate-induced hyperlocomotion (MIH) test; in this assay valproate was used as positive control. The G protein and β-arrestin 2 transduction pathways of NOP receptor agonists (N/OFQ and Ro 65-6570), antagonist (UFP-101), and partial agonists (UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090) were also evaluated using an innovative assay that measures a bioluminescence resonance energy transfer process. For this, cell lines permanently co-expressing the NOP receptor coupled to luciferase (energy donor), and green fluorescent protein (energy acceptor) coupled to one of the effector proteins (G protein or β-arrestin 2) were used. Results: Diazepam (1 mg/kg), N/OFQ (1 nmol), Ro 65-6570 (0.1 mg/kg), and AT-090 (0.01 mg/kg) induced anxiolytic-like effect in mice in the EPM. The effects of Ro 65-6570 and AT-090 were selective to NOP receptor. UFP-113 (0.01-1 nmol) and [F/G]N/OFQ(1-13)NH2 (0.1-3 nmol) were inactive in the EPM. In the FST, nortriptyline (30 mg/kg), UFP-101 (10 nmol), SB-612111 (10 mg/kg), UFP-113 (0.01 and 0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (0.3 and 1 nmol) induced antidepressant-like effects, while AT-090 (0.001-0.1 mg/kg) was inactive in this assay. The effects of UFP-113 and [F/G]N/OFQ(1-13)NH2 were selective to NOP receptor. Valproate (400 mg/kg) counteracted methylphenidate (MPH, 10 mg/kg)-induced hyperlocomotion in mice in the open field. N/OFQ (1 nmol), UFP-113 (0.01-0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (1 nmol) were also able to reduce the MPH-induced hyperlocomotion, without changing the locomotor activity per se. The effect of UFP-113 was selective to NOP receptor. The UFP-101 (10 nmol), SB-612111 (10 mg/kg), and AT-090 (0.001-0.03 mg/kg) did not change the hyperlocomotor effect of methylphenidate. In vitro, N/OFQ and Ro 65-6570 behaved as NOP full agonists for G-protein and β-arrestin 2 pathways. AT-090 behaved as NOP receptor partial agonist for both transduction pathways, while UFP-113 and [F/G]N/OFQ(1-13)NH2 behaved as partial agonists and antagonists of NOP receptor for NOP/G protein and NOP/β-arrestin 2, respectively. UFP-101 behaved as NOP receptor antagonist for both transduction pathways. Conclusion: NOP ligands producing same effects on NOP/G protein interaction (partial agonism), but with opposite effects on β-arrestin 2 recruitment (partial agonism vs antagonism), can promote different in vivo effects on anxiety and mood as it was observed in the behavioral tests. This work corroborates the potential of NOP receptor as an innovative pharmacological target for the treatment of emotional disorders.

Efeitos in vivo e in vitro de agonistas parciais do receptor NOP: implicações para o tratamento da ansiedade, depressão e mania

Introduction: This study aimed to investigate the effects of the two peptide NOP partial agonists (UFP-113 and [F/G]N/OFQ(1-13)NH2) and the non peptide NOP partial agonist (AT-090) in the mouse emotional behavior as well as in the intracellular transduction pathways following the receptor binding. Methods: Male Swiss or CD-1 mice were used in this study together with NOP(+/+) and NOP(-/-) mice. The elevated plus maze (EPM) was used to evaluate the effects of compounds on anxiety-like behaviors. Diazepam and the NOP agonists, N/OFQ and Ro 65-6570, were used as positive controls in the EPM. NOP(+/+) and NOP(-/-) mice were used to evaluate the selectivity of those compounds that induced anxiolytic-like behaviors. The forced swim test (FST) was used to evaluate the effects of compounds on depressive-like behaviors. Nortriptyline and the NOP antagonists, UFP-101 and SB-612111, were used as positive controls in the FST. The effects of N/OFQ, UFP-101, SB-612111, UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090 were assessed in the methylphenidate-induced hyperlocomotion (MIH) test; in this assay valproate was used as positive control. The G protein and β-arrestin 2 transduction pathways of NOP receptor agonists (N/OFQ and Ro 65-6570), antagonist (UFP-101), and partial agonists (UFP-113, [F/G]N/OFQ(1-13)NH2, and AT-090) were also evaluated using an innovative assay that measures a bioluminescence resonance energy transfer process. For this, cell lines permanently co-expressing the NOP receptor coupled to luciferase (energy donor), and green fluorescent protein (energy acceptor) coupled to one of the effector proteins (G protein or β-arrestin 2) were used. Results: Diazepam (1 mg/kg), N/OFQ (1 nmol), Ro 65-6570 (0.1 mg/kg), and AT-090 (0.01 mg/kg) induced anxiolytic-like effect in mice in the EPM. The effects of Ro 65-6570 and AT-090 were selective to NOP receptor. UFP-113 (0.01-1 nmol) and [F/G]N/OFQ(1-13)NH2 (0.1-3 nmol) were inactive in the EPM. In the FST, nortriptyline (30 mg/kg), UFP-101 (10 nmol), SB-612111 (10 mg/kg), UFP-113 (0.01 and 0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (0.3 and 1 nmol) induced antidepressant-like effects, while AT-090 (0.001-0.1 mg/kg) was inactive in this assay. The effects of UFP-113 and [F/G]N/OFQ(1-13)NH2 were selective to NOP receptor. Valproate (400 mg/kg) counteracted methylphenidate (MPH, 10 mg/kg)-induced hyperlocomotion in mice in the open field. N/OFQ (1 nmol), UFP-113 (0.01-0.1 nmol), and [F/G]N/OFQ(1-13)NH2 (1 nmol) were also able to reduce the MPH-induced hyperlocomotion, without changing the locomotor activity per se. The effect of UFP-113 was selective to NOP receptor. The UFP-101 (10 nmol), SB-612111 (10 mg/kg), and AT-090 (0.001-0.03 mg/kg) did not change the hyperlocomotor effect of methylphenidate. In vitro, N/OFQ and Ro 65-6570 behaved as NOP full agonists for G-protein and β-arrestin 2 pathways. AT-090 behaved as NOP receptor partial agonist for both transduction pathways, while UFP-113 and [F/G]N/OFQ(1-13)NH2 behaved as partial agonists and antagonists of NOP receptor for NOP/G protein and NOP/β-arrestin 2, respectively. UFP-101 behaved as NOP receptor antagonist for both transduction pathways. Conclusion: NOP ligands producing same effects on NOP/G protein interaction (partial agonism), but with opposite effects on β-arrestin 2 recruitment (partial agonism vs antagonism), can promote different in vivo effects on anxiety and mood as it was observed in the behavioral tests. This work corroborates the potential of NOP receptor as an innovative pharmacological target for the treatment of emotional disorders.

Qual é a sua tribo? O uso do TAI online no desvelamento de conhecimentos sociais ocultos

The Implicit Association Test (IAT) has succeeded in accessing mental phenomena hardly exposed through self-report and explicit measures well known in the traditional studies on psychology. Although this measurement technique is among the most consistent in international publications, the few articles in Brazil have not deepened on theoretical issues that underlie the practice. This created a gap between the spread of this measure in the country and the production seen in international laboratories, both at quantitative and qualitative terms. In this context, the online labs implemented in several countries, including Brazil, created unique opportunities to overcome these disparities. Our work sought theoretical and conceptual clarification, contextualized to the historical development of the IAT and its online version, displaying affordably an unprecedented presentation of the virtual tool adapted to the Brazilian public. In a second step, we investigated empirically the data obtained by the Brazilian electronic portal "Countries", analyzing the degree of implicit and explicit nationalism of 2271 Brazilian subjects collected from early 2009 to late 2014. Our goal was to determine whether the data results obtained in a time of major sporting confrontation (FIFA World Cup 2010 and 2014) differ from periods when the tournament did not happen. Analyzes showed differences on the eve of the sporting confrontation, when the increase in the implicit nationalism was clearly superior, even with no effect by self-reports. In an independent analysis of a cultural context, there is an oscillation of explicit nationalism over the years, but not for the implicit action. In addition, it was found in women greater degree of implicit and explicit nationalism than in men, with both sexes presenting their preferences towards Brazil. In an end section, we suggest that nationalism may be a by-product of universal mental mechanisms that evolved to identify of the belonging group categorization, corroborating with the group favoritism. We propose that the intensification of the group preference on the eve of the competition has as its ancestral function strengthen the cohesion of the group in preparation to confrontational situations. We pointed out the need for studies on the differences between the sexes in matters relating to group membership belonging. It was expected largest nationalist attitudes in men reflecting the maintenance of cohesive groups in ancient societies. Thus, it appears a singular importance impart the traditional TAI studies with its online version for future investigations of human behavior in various areas of knowledge.

Qual é a sua tribo? O uso do TAI online no desvelamento de conhecimentos sociais ocultos

The Implicit Association Test (IAT) has succeeded in accessing mental phenomena hardly exposed through self-report and explicit measures well known in the traditional studies on psychology. Although this measurement technique is among the most consistent in international publications, the few articles in Brazil have not deepened on theoretical issues that underlie the practice. This created a gap between the spread of this measure in the country and the production seen in international laboratories, both at quantitative and qualitative terms. In this context, the online labs implemented in several countries, including Brazil, created unique opportunities to overcome these disparities. Our work sought theoretical and conceptual clarification, contextualized to the historical development of the IAT and its online version, displaying affordably an unprecedented presentation of the virtual tool adapted to the Brazilian public. In a second step, we investigated empirically the data obtained by the Brazilian electronic portal "Countries", analyzing the degree of implicit and explicit nationalism of 2271 Brazilian subjects collected from early 2009 to late 2014. Our goal was to determine whether the data results obtained in a time of major sporting confrontation (FIFA World Cup 2010 and 2014) differ from periods when the tournament did not happen. Analyzes showed differences on the eve of the sporting confrontation, when the increase in the implicit nationalism was clearly superior, even with no effect by self-reports. In an independent analysis of a cultural context, there is an oscillation of explicit nationalism over the years, but not for the implicit action. In addition, it was found in women greater degree of implicit and explicit nationalism than in men, with both sexes presenting their preferences towards Brazil. In an end section, we suggest that nationalism may be a by-product of universal mental mechanisms that evolved to identify of the belonging group categorization, corroborating with the group favoritism. We propose that the intensification of the group preference on the eve of the competition has as its ancestral function strengthen the cohesion of the group in preparation to confrontational situations. We pointed out the need for studies on the differences between the sexes in matters relating to group membership belonging. It was expected largest nationalist attitudes in men reflecting the maintenance of cohesive groups in ancient societies. Thus, it appears a singular importance impart the traditional TAI studies with its online version for future investigations of human behavior in various areas of knowledge.

Efeitos da privação do sono em tarefas cognitivas

Learning and memory are important mechanism for species, since its allows to recognize conspecifics, routes and food place. Sleep is one of behaviors known by facilitate learning, it is a widespread phenomenon, present in most of vertebrates lives and highly investigated in many aspects. It is known that sleep deprivation modifies physiologic behavioral processes in animals, however, sleep function in organism is still debatable. Hypothesis range from energy conservation to memory consolidation, with different roles in animal’s evolution. The zebrafish (Danio rerio) emerg e in the last years as vertebrate model in genetics and developmental biology and quickly become popular in behavioral studies, as learning and memory. Despite the fact that zebrafish is a diurnal animal and have well characterized sleep behavior, zebrafish fish still has advantages due to its small size and low cost of maintenance, whichestablishes this species as interesting model for research on sleep. In this study we aimed to analyze the effects of partial and total sleep deprivation on learning acquisition, as well the concomitant administration of alcohol and melatonin. For this, the research was divided in three phases, each one with a different kind of conditioning: (1) object Recognition, (2) avoidance conditioning and (3) appetitive conditioning. The results showed the fish partially sleep deprived and totally sleep deprived + et hanol could perform the tasks just like the control group, however, fish totally sleep deprived and totally sleep deprived + melatonin showed impairments in attention and memory during the tests. Our results suggest that only one night of sleep deprivation is enough to harm the zebrafish performance in cognitive tasks. In addition, ethanol exposure on the night previously the test seems to suppress the negative effects of sleep deprivation, while the melatonin treatment seems not to be enough to promote sleep state, at least on the protocol applied here.

Efeitos da privação do sono em tarefas cognitivas

Learning and memory are important mechanism for species, since its allows to recognize conspecifics, routes and food place. Sleep is one of behaviors known by facilitate learning, it is a widespread phenomenon, present in most of vertebrates lives and highly investigated in many aspects. It is known that sleep deprivation modifies physiologic behavioral processes in animals, however, sleep function in organism is still debatable. Hypothesis range from energy conservation to memory consolidation, with different roles in animal’s evolution. The zebrafish (Danio rerio) emerg e in the last years as vertebrate model in genetics and developmental biology and quickly become popular in behavioral studies, as learning and memory. Despite the fact that zebrafish is a diurnal animal and have well characterized sleep behavior, zebrafish fish still has advantages due to its small size and low cost of maintenance, whichestablishes this species as interesting model for research on sleep. In this study we aimed to analyze the effects of partial and total sleep deprivation on learning acquisition, as well the concomitant administration of alcohol and melatonin. For this, the research was divided in three phases, each one with a different kind of conditioning: (1) object Recognition, (2) avoidance conditioning and (3) appetitive conditioning. The results showed the fish partially sleep deprived and totally sleep deprived + et hanol could perform the tasks just like the control group, however, fish totally sleep deprived and totally sleep deprived + melatonin showed impairments in attention and memory during the tests. Our results suggest that only one night of sleep deprivation is enough to harm the zebrafish performance in cognitive tasks. In addition, ethanol exposure on the night previously the test seems to suppress the negative effects of sleep deprivation, while the melatonin treatment seems not to be enough to promote sleep state, at least on the protocol applied here.