Efeitos da cafeína sobre a memória de saguis (Callithrix jacchus)

Caffeine is considered the most consumed psychostimulant in the world, presenting several central and peripheral effects. In the Central Nervous System the major effect occur by its antagonistic activity at the A1 and A2a subtypes of the adenosine receptors. These receptors are responsible for the slow-wave sleep induction, and their binding, caused by the consumption of foods and beverages that contain caffeine, cause behaviors like increase of alertness, mood and locomotion. The effects of caffeine on memory are still discussed because of the diversity of experimental protocols. Also, it does not have the same effects on all stages of the processing of memory - acquisition, consolidation and recall. Thus, using the marmoset (Callitrhix jacchus) as subject, we aim to evaluate the effects of caffeine on the memory of this primate through the conditioned place preference paradigm, where the animal selects a context by presence of food. This cognitive task consists of five phases. The first phase was two sessions of pre-exposure, in which they were evaluated for preference for any compartment of the apparatus. Then, we proceeded the training, conditioning the animals to the food-present context for 8 days. Then, there was administration of caffeine or placebo (10mg/kg) for 8 consecutive days, during the pre-sleep phase, where the 20 animals were distributed in two groups: placebo and repeated. The forth phase was one day of retraining, a re-exposure of the apparatus to the marmosets followed by the administration of caffeine (for the repeated group and a new group called abstinence) or placebo (for placebo and abstinence groups). Finally, was the test where we evaluated if the subjects learned where the food was present. Moreover, in this work we evaluate the existence of differences between females and males on the task, and the locomotor activity for the experimental groups. The results showed that in the pre-exposure phase the animals were habituated on the apparatus and did not present differences for any contexts. In training, they were able to learn the conditioning task, independent of gender. For the retraining, the two groups exhibited more interactions in rewarded context than that in non-rewarded context. Nevertheless, in the locomotor activity, the repeated group moved similarly in contact with the apparatus and outside of it. In the other hand, the animals of the placebo group moved more when in contact with the apparatus. In the test phase, the marmosets under influence of caffeine presented an increase in the locomotor activity when compared with the placebo group, corroborating works that show this increase in locomotion. In the learning evaluation, the continuous and abstinence groups had a bad performance in the task in relation to the placebo and acute groups. This suggests that the prolonged administration of caffeine disrupts the memories because it affected sleep, which is largely responsible offline processing of memories

Participação da neurotransmissão dopaminergica no efeito hiperlocomotor do neuropeptideo S

Neuropeptide S (NPS) is an endogenous 20-aminoacid peptide which binds a G protein-coupled receptor named NPSR. This peptidergic system is involved in the modulation of several biological functions, such as locomotion, anxiety, nociception, food intake and motivational behaviors. Studies have shown the participation of NPSR receptors in mediating the hyperlocomotor effects of NPS. A growing body of evidence suggests the participation of adenosinergic, dopaminergic and CRF systems on the hyperlocomotor effects of NPS. Considering that little is known about the role of dopaminergic system in mediating NPS-induced hyperlocomotion, the present study aims to investigate the locomotor actions of intracerebroventricular (icv) NPS in mice pretreated with α-metil-p-tirosine (AMPT, inhibitor of dopamine synthesis), reserpine (inhibitor of dopamine vesicle storage) or sulpiride (D2 receptor antagonist) in the open field test. A distinct group of animals received the same pretreatments described above (AMPT, reserpine or sulpiride) and the hyperlocomotor effects of methylphenidate (dopamine reuptake inhibitor) were investigated in the open field. NPS and methylphenidate increased the mouse locomotor activity. AMPT per se did not change the locomotion of the animals, but it partially reduced the hyperlocomotion of methylphenidate. The pretreatment with AMPT did not affect the psychostimulant effects of NPS. Both reserpine and sulpiride inhibited the stimulatory actions of NPS and methylphenidate. These findings show that the hyperlocomotor effects of methylphenidate, but not NPS, were affected by the pretreatment with AMPT. Furthermore, methylphenidate- and NPS-induced hyperlocomotion was impaired by reserpine and sulpiride pretreatments. Together, data suggests that NPS can increase locomotion even when the synthesis of catecholamines was impaired. Additionally, the hyperlocomotor effects of NPS and methylphenidate depend on monoamines vesicular storaged, mainly dopamine, and on the activation of D2 receptors. The psychostimulant effects of NPS via activation of dopaminergic system display clinical significance on the treatment of diseases which involves dopaminergic pathways, such as Parkinson s disease and drug addiction

Efeitos do tratamento com lítio na memória aversiva, comportamentos relacionados à ansiedade e depressão e na expressão de BDNF em ratos

Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.

Pressão de sono e perfil acadêmico de estudante de medicina do 1º período da UFRN

Academic demands, new social context, new routines and decrease of the parental control, are factors that may influence the sleep pattern of freshman students at the University. Medical students from the Federal University of Rio Grande do Norte (UFRN) have a full-time course, subjects with high-level content, and, at the first semester, classes begin at 7 a.m. This group composed by young adults who still suffering with delayed sleep phase, common in adolescence, indicating that this class schedule can be inappropriate at this age. The reduction of nocturnal sleep during school days, and the attempt to recover sleep on free days – social jet lag (JLS), suggests that in the first semester, students suffer from high sleep pressure. High sleep pressure may reflect on cognitive tasks and performance. Therefore, the aim of this study was to investigate the relationship between sleep pressure and the academic profile of medical students from the first semester of UFRN, characterizing this population socio-demographically and investigating possible impacts on therestactivity rhytm and academic performance. A sample of 88 students, healthy men and women awswered the following questionnaires: Pittsburgh Sleep Quality (PSQI), Epworth Sleepiness Scale (ESS), Horne & Ostberg Chronotype (HO), Munich Chronotype (MCTQ) and “Health and Sleep” adapted. Actigraphy was used during 14 days to make actogramas and obtain non-parametric variables of the rest-activity rhythm and the grades of the morning schedule were used as academic performance. The JLS was used as a measure of sleep pressure. Statistics significance level was 95%. The population was sociodemographic homogeneous. Most students have healthy lifestyle, practice physical activity, use car to go to the university and take between 15 and 30 minutes for this route. Regarding CSV, most were classify as intermediate (38.6%) and evening (32%) chronotypes, needs to nap during the week, suffer daytime sleepiness and have poor sleep quality. 83% of the sample has at least 1h JLS, which led us to divide into two groups: Group <2h JLS (N = 44) and Group ≥ 2h JLS (N = 44). The groups have differences only in chronotype, showing that most evening individuals have more JLS, however, no differences were found in relation to sociodemographic aspect, rest-activity rhythm or academic performance. The homogeneity of the sample was limited to compare the groups, however, is alarming that students already present in the first half: JLG, poor sleep quality and excessive daytime sleepiness, which can be accentuated through the university years, with the emergence of night shifts and increased academic demand. Interventionsaddressingthe importance of good sleep habits and the change of the class start time are strategies aimed to improve student’s health.

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.

Irish Coffee: efeitos de álcool e cafeína no comportamento e aprendizagem do peixe paulistinha

Substâncias psicoestimulantes vêm sendo utilizadas de forma indiscriminada há muitos anos, e pouco se sabe os efeitos que elas causam a curto e longo prazo no comportamento geral, na aprendizagem e na memória. Essas substâncias são bastante usadas por jovens e adultos e elas possuem efeitos diferentes. Essas substâncias são dose dependente, caso consumidas em baixa quantidade agem como estimulante, aumentando a atividade locomotora, caso consumidas em alta quantidade, causam efeito depressor, diminuindo a atividade locomotora e/ou causando ansiedade. Poucos estudos vêm investigando os efeitos dessas substâncias na atividade locomotora, aprendizagem e memória e grande parte desses estudos são realizados em roedores. Peixe paulistinha é um modelo animal promissor para estudos comportamentais, cognitivos, ontogenéticos, dentre outros. Nossos objetivos foram determinar os efeitos do álcool, cafeína e de seu uso combinado com álcool, na atividade locomotora desses animais, usando para isso doses crônicas durante 27 dias e doses agudas durante um dia. Visto que pouco se sabe sobre os efeitos dessa exposição prolongada. Também investigamos os efeitos das substâncias em teste de reconhecimento de objetos, que se baseia na memória de único evento. Essas memórias são mais vulneráveis que memórias baseadas em várias repetições de eventos. Sendo assim, um teste adequado para utilizar com uso de substâncias psicoativas. Observamos que o uso crônico de cafeína provoca alteração na atividade locomotora dos animais, do mesmo modo, abstinência de álcool combinada com cafeína em dose aguda (dose média) provoca aumento de atividade locomotora. Quando submetidos a testes de memória, os animais exposto a doses altas agudas de álcool e em abstinência dessa droga têm prejuízo na formação e/ou resgate da memória. No entanto, tratamento com cafeína não prejudica a formação de memória. Animais expostos a tratamento com dose crônica moderada de álcool e dose aguda moderada de cafeína tem melhor desempenho na tarefa, indicando que dose aguda moderada de cafeína pode evitar os efeitos deletérios ocasionados pela abstinência do álcool. Em termos do comportamento geral, doses agudas de cafeína aumentam a locomoção, enquanto doses elevadas e a abstinência de cafeína induzem a comportamentos tipo-ansioso. A combinação álcool crônico e cafeína aguda induzem a alto comportamento tipo-ansiedade, enquanto a combinação cafeína crônica e álcool agudo diminuem tanto a locomoção quanto a ansiedade.

Irish Coffee: efeitos de álcool e cafeína no comportamento e aprendizagem do peixe paulistinha

Substâncias psicoestimulantes vêm sendo utilizadas de forma indiscriminada há muitos anos, e pouco se sabe os efeitos que elas causam a curto e longo prazo no comportamento geral, na aprendizagem e na memória. Essas substâncias são bastante usadas por jovens e adultos e elas possuem efeitos diferentes. Essas substâncias são dose dependente, caso consumidas em baixa quantidade agem como estimulante, aumentando a atividade locomotora, caso consumidas em alta quantidade, causam efeito depressor, diminuindo a atividade locomotora e/ou causando ansiedade. Poucos estudos vêm investigando os efeitos dessas substâncias na atividade locomotora, aprendizagem e memória e grande parte desses estudos são realizados em roedores. Peixe paulistinha é um modelo animal promissor para estudos comportamentais, cognitivos, ontogenéticos, dentre outros. Nossos objetivos foram determinar os efeitos do álcool, cafeína e de seu uso combinado com álcool, na atividade locomotora desses animais, usando para isso doses crônicas durante 27 dias e doses agudas durante um dia. Visto que pouco se sabe sobre os efeitos dessa exposição prolongada. Também investigamos os efeitos das substâncias em teste de reconhecimento de objetos, que se baseia na memória de único evento. Essas memórias são mais vulneráveis que memórias baseadas em várias repetições de eventos. Sendo assim, um teste adequado para utilizar com uso de substâncias psicoativas. Observamos que o uso crônico de cafeína provoca alteração na atividade locomotora dos animais, do mesmo modo, abstinência de álcool combinada com cafeína em dose aguda (dose média) provoca aumento de atividade locomotora. Quando submetidos a testes de memória, os animais exposto a doses altas agudas de álcool e em abstinência dessa droga têm prejuízo na formação e/ou resgate da memória. No entanto, tratamento com cafeína não prejudica a formação de memória. Animais expostos a tratamento com dose crônica moderada de álcool e dose aguda moderada de cafeína tem melhor desempenho na tarefa, indicando que dose aguda moderada de cafeína pode evitar os efeitos deletérios ocasionados pela abstinência do álcool. Em termos do comportamento geral, doses agudas de cafeína aumentam a locomoção, enquanto doses elevadas e a abstinência de cafeína induzem a comportamentos tipo-ansioso. A combinação álcool crônico e cafeína aguda induzem a alto comportamento tipo-ansiedade, enquanto a combinação cafeína crônica e álcool agudo diminuem tanto a locomoção quanto a ansiedade.

Ritmo circadiano de atividade motora e distribuição diária dos comportamentos afiliativos ao longo da fase juvenil em saguis (callithrix jacchus)

The temporal allocation of the active phase in relation to light and dark cycle (LD) changes during puberty in humans, degus, rats and rhesus. In marmosets, the animal model used in several biomedical researches, there is evidence of a delay at the beginning of the active phase and an increase in total daily activity after onset of puberty. However, as this aspect was evaluated in animals maintained in natural environmental conditions, it was not possible to distinguish between the effects of puberty and of seasonality. Furthermore, as motor activity is the result of different behaviors in this species, it is also important to characterize the diurnal distribution of other behaviors in juvenile stage. With the aim of characterizing the circadian rhythm of motor activity and the diurnal profile of affiliative behavior in marmosets, the motor activity of 5 dyads juveniles between 4 and 12 months of age and their parents was recorded continuously for actímetro. The families were maintained under artificial LD 12:12 h, constant temperature and humidity. The duration of grooming behavior, proximity and social play among juveniles was recorded 2 times a week in sessions of 15 minutes each hour of the active phase. Afetr onset of puberty in juvenile, it was observed that there was no change in the parameters of circadian motor activity rhythm which were common to most animals. Despite the absence of pubertal modulation, it was observed that the circadian activity profiles have stronger synchrony between individuals of the same family than that of different families, which may indicate that the circadian activity rhythm was modulated by the dynamics of social interactions. In relation to age, the total daily activity and the ratio between evening and morning activity (EA/MA) were higher in juveniles than in adults, which may be associated with differences in the circadian timing system between age groups. Furthermore, the onset of the 10 consecutive hours of higher activity (M10) occurred earlier in adult males than in other members of the group, probably as a way to avoid competition for resources in one of the first activities of the day that is foraging. During the juvenile stage, there was an increase in total daily activity that may be associated with increased motor ability of juveniles. In addition to the circadian activity rhythm, the daytime profile of proximity and social play behaviors was similar between the 5th and 12th month of life of juveniles, in which the interval between 7- 10 h in the morning showed the highest values of proximity and lower values of play social. Moreover, the duration of the grooming showed a similar distribution to adults from the 8th month, wherein the higher values occurring at the interval between 11 14 h of day. Considering the results, the parameters of the circadian activity rhythm had a greater influence of social factors than puberty. In relation to age, there were no changes related to the allocation of the active phase in relation to the LD cycle, but total daily activity, the ratio AV/AM and the start of the M10 is possible to observe differences between juveniles and adults

Efeitos de vocalizações de co-específicos e do escuro sobre o ritmo circadiano da atividade motora em sagüis (Callithrix jacchus)

The principal zeitgeber for most of species is the light-dark photocycle (LD), though other environment factors as food availability, temperature and social cues may act. Daily adjustment of the circadian pacemaker may result from integration of environmental photic and non-photic cues with homeostatic cues. Characterization of non-photic effects on circadian timing system in diurnal mammals is scarce in relation to nocturnal, especially for ecologically significant cues. Thus, we analyzed the effect of conspecific vocalizations and darkness on circadian activity rhythm (CAR) in the diurnal primate Callithirx jacchus. With this objective 7 male adults were isolated in a room with controlled illumination, temperature (26,8 ± 0,2°C) and humidity (81,6 ± 3,6%), and partial acoustic isolation. Initially they were under LD 12:12 (~300:2 lux), and subsequently under constant illumination (~2 lux). Two pulses of conspecific vocalizations were applied in total darkness, separated by 22 days, at 7:30 h (external time) during 1 h. They induced phase delays at circadian times (CTs) 1 and 10 and predominantly phase advances at CTs 9 and 15. After that, two dark pulses were applied, separated by 14 days, during 1 h at 7:30 h (external time). These pulses induced phase delays at CTs 2, 3 and 18, predominantly phase advances at CTs 8, 10 and 19, and no change at CT 14. However, marmosets CAR showed oscillations in endogenous period and active phase duration influenced by vocalizations from animals outside the experimental room, which interfered on the phase responses to pulses. Furthermore, social masking and relative coordination with colony were observed. Therefore, phase responses obtained in this work cannot be attributed only to pulses. Afterwards, pulses of conspecific vocalizations were applied in total darkness at 19:00 h (external time), during 1 h for 5 consecutive days, and after 21 days, for 30 consecutive days, on attempt to synchronize the CAR. No animal was synchronized by these daily pulses, although oscillations in endogenous period were observed for all. This result may be due to habituation. Other possibility is the absence of social significance of the vocalizations for the animals due to random reproduction, since each vocalization has a function that could be lost by a mixture of sounds. In conclusion, conspecific vocalizations induce social masking and relative coordination in marmosets CAR, acting as weak zeitgeber

Influência da auto seleção à luz no ritmo circadiano de atividade motora em Callithrix Jacchus

Marmosets, Callithrix jacchus, are strictly diurnal animals. The motor activity rhythmicity is generated by the circadian timing system and is modulated by environmental factors, mainly by photic stimuli that compose the light-dark cycle. Photic stimuli can reset the biological oscilators changing activity motor pattern, by a mechanism called entrainment. Otherwise, light can act directly on expressed rhythm, without act on the biological oscillators, promoting the masking. Thus, photic stimuli can synchronize the circadian activity rhythm (CAR) by two distinct mechanisms, acting isolated or at a combined way. Among the elements that can influence photic synchronization, the duration and time of photic exposure is pointed out. If in the natural environment the marmoset can choose places of different intensity illumination and is synchronized to light-dark cycle (LD), how the photic synchronization mechanism can be evaluated in laboratory by light self-selection? With objective to response this question, four adult male marmosets were studied at two conditions: with and without sleeping box. The animals were submitted to a LD cycle (12:12/ 350:2 lx) and constant light (LL: 350 lx) conditions in individual cages with an opaque sleeping box, that permitted the light self-selection. At the room, the temperature was 25.6 ºC (± 0.3 ºC) and humidity was 78.7 (± 5%). The motor activity was recorded at 5 min bins by infrared movement sensors installed at the top of the cages. The motor activity profile was distinct at the two conditions: without the sleeping box protection against light, the activity frequency was higher at CT 11-12 (ANOVA; F(3.23) = 62.27; p < 0.01). Also, the duration of the active phase (α) was prolonged of about 1 h (t test, p < 0.05) and the animals showed a significant delay on the activity onset and offset (t test, p < 0.05) and at the acrophase (confidence intervals of 5%) of CAR. In LL, the light continuous exposure prolonged the active phase and influenced the endogenous expression of the circadian activity rhythm period. From the result analysis, it is concluded that the light self-selection can modify several parameters of CAR in marmosets, allowing the study of the synchronization mechanism using the burrow model. Thus, without sleeping box there was a phase delay between the CAR and LD (entrainment) and an increase of activity near lights off (positive masking). Furthermore, in LL, the light continuous exposure modifies α and the endogenous expression of CAR. It is suggested that the light self-selection might be take into account at investigations that evaluate the biological rhythmicity in marmosets

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.

Controle circadiano e homeostático do sono-virgília em pacientes com acidente vascular encefálico e correlações com a qualidade de vida e o nível de atividade física

The cerebral vascular accident is a neurological dysfunction of vascular origin that leds to development of motor sensibility, cognitive, perceptive and language deficits. Despite the fact that the main sleep disorders in stroke patients are well known, it is still necessary to analyze which mechanisms of regulation of sleep and wakefulness are affected. The objective of this study was to evaluate the changes in the circadian and homeostatic control of sleep-wakefulness in stroke patients and the correlations with quality of life and level of physical activity. The study analyzed 22 stroke patients (55± 12 years old) and 24 healthy subjects (57 ±11 years old). The instruments used in this study were questionnaires on sleep quality, daytime sleepiness, quality of life, physical activity level and the actigraphy. The data were analyzed using the Student `t test, Mann-Whitney test, ANOVA and Spearman's correlation tests. The results showed stability in the sleep-wake circadian expression with changes in the amplitude of the rhythm. However, significant changes were found related to the homeostatic component characterized by increased sleep duration, increased latency, fragmented sleep and lower sleep efficiency. Additional data showed decreased quality of sleep and increased daytime sleepiness, as well as decreased quality of life and level of physical activity. The results indicate that the interaction of circadian and homeostatic control of sleep-wake is compromised and the main reason might be because of the homeostatic component and the lower activity level resulting from the brain damage. Thus, further studies may be developed to evaluate whether behavioral interventions such as increased daytime activity and restriction of sleep during the day can influence the homeostatic process and its relation to circadian component, resulting in improved quality of nocturnal sleep in stroke patients

Caracaterização do núcleo pré-geniculado do sagüi (Callithrix jacchus) :projeção retiniana, neuroquímica e atividade celular (expressão de FOS)

In rodents, the suprachiasmatic nucleus (SCN) and the intergeniculate leaflet (IGL) are the main components of the circadian system. The SCN is considerate the site of an endogenous biological clock because can to generate rhythm and to synchronize to the environmental cues (zeitgebers) and IGL has been related as one of the main areas that modulate the action of SCN. Both receive projections of ganglion cells of retina and this projection to SCN is called retinohypothalamic tract (RHT). Moreover, the IGL is connected with SCN through of geniculohypothalamic tract (GHT). In primates (include humans) was not still demonstrated the presence of a homologous structure to the IGL. It is believed that the pregeniculate nucleus (PGN) can be the answer, but nothing it was still proven. Trying to answer that question, the objective of our study is to do a comparative analysis among PGN and IGL through of techniques immunohystochemicals, neural tracers and FOS expression after dark pulses. For this, we used as experimental model a primate of the new world, the common marmoset (Callithrix jacchus). Ours results may contribute to the elucidation of this lacuna in the circadian system once that the IGL is responsible for the transmission of nonphotic information to SCN and participate in the integration between photic and nonphotic stimulus to adjust the function of the SCN. In this way to find a same structure in primates represent an important achieve in the understanding of the biological rhythms in those animals