Amphetamine- and nicotine-induced cross-sensitization in adolescent rats persists until adulthood

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Stress-induced reinstatement of amphetamine-conditioned place preference and changes in tyrosine hydroxylase in the nucleus accumbens in adolescent rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influência de fatores individuais e sociais sobre as respostas endócrina e comportamental de callithrix jacchus a desafios ambientais físicos e sociais

Regarding the growing number of human beings with physical and mental pathologies associated to different stressor agents, attempts are being made to validate animal models with a close phylogenetic resemblance to man, to study stress response. Callithrix jacchus has been widely used in biomedical research, including on stress, but there is scarce information in the literature about how individual and social factors modulate stressor response in this species. This study uses 4 approaches to investigate the response of male and female adult C. jacchus, under situations of stress, and in the first we show evidence of the importance of this animal as an experimental model in research involving the hypothalamus-pituitary-adrenal axis. And we investigate if sex and baseline cortisol levels modulate the behavioral and hormonal response to separation. In two additional approaches investigate if type of social support (co-specific parent or non-parent) and social rank interfere in behavioral and hormonal when the animal are exposure to a new environment, paired with a co-specific (F2), exposure of the animal to a new environment, isolated (F3) or during reunion (F4). Finally, we also investigated the androgen levels in the males, with a focus on the challenge hypothesis, referring to environmental responsiveness and male-male exposure to relatives and non-relatives of C. jacchus. It was observed that: (1) the baseline cortisol of the animal is predictive of cortisol reactivity at separation; (2) males and females do not show dimorphism in the response of cortisol to stressors, although the females have higher baseline levels of this hormone and exhibit higher frequencies of anxiety-related behaviors; (3) only social support provided by relatives proved to be effective in buffering the cortisol response. In behavioral terms this response was dimorphic, showing that only the male dyads displayed an attenuated response to stress; (4) the males showed differences in cortisol levels as a function of social rank and study phases, whereas in the females no such alterations were observed. The males with indefinite dominance hierarchy (IDH) had reduced cortisol in F2 and F4, while the IDH females showed an increase in F3 and F4; (5) the males of relative and non-relative dyads did not exhibit variations in androgen levels as a function of a new environment. These results, taken together, (a) corroborate the use of C. jacchus as a good animal model for stress-related studies, given that they exhibit similar behavioral and physiological alterations to those of human beings in response to stressor agents; (b) point to the importance of considering individual and social modulating factors during experiments with stressors; (c) provide more reliable comparison parameters in studies where these primates are used as animal models, and (d) show that androgens vary as a function of genetic proximity (relative or non-relative) when the animals are faced with physical and social environmental challenges, thus providing important information for studying the challenge hypothesis in this species

Administração repetida de baixas doses de reserpina: um possível modelo para o estudo de déficits cognitivos e motores associados à Doença de Parkinson

Parkinson's disease (PD) is one of the most common neurodegenerative brain disorders and is characterized primarily by a progressive degeneration of dopaminergic neurons nigroestriatais. The main symptoms of this disease are motor alterations (bradykinesia, rigidity, tremor at rest), which can be highly disabling in advanced stages of the condition. However, there are symptomatic manifestations other than motor impairment, such as changes in cognition, mood and sensory systems. Animal models that attempt to mimic clinical features of PD have been used to understand the behavioral and neural mechanisms underlying neurophysiological disturbance of this disease. However, most models promote an intense and immediate motor impairment, consistent with advanced stages of the disease, invalidating these studies for the evaluation of its progressive nature. The administration of reserpine (a monoamine depletor) in rodents has been considered an animal model for studying PD. Recently we found that reserpine (in doses lower than those usually employed to produce the motor symptoms) promotes a memory deficit in an aversive discrimination task, without changing the motor activity. It was suggested that the administration of this drug in low doses can be useful for the study of memory deficits found in PD. Corroborating this data, in another study, acute subcutaneous administration of reserpine, while preserving motor function, led to changes in emotional context-related (but not neutral) memory tasks. The goal of this research was to study the cognitive and motor deficits in rats repeatedly treated with low doses of reserpine, as a possible model that simulates the progressive nature of the PD. For this purpose, 5-month-old male Wistar rats were submitted to a repeated treatment with vehicle or different doses of reserpine on alternate days. Cognitive and motor parameters and possible changes in neuronal function were evaluated during treatment. The main findings were: repeated administration of 0.1 mg / kg of reserpine in rats is able to induce the gradual appearance of motor signs compatible with progressive features found in patients with PD; an increase in striatal levels of oxidative stress and changes in the concentrations of glutamate in the striatum were observed five days after the end of treatment; in animals repeatedly-treated with 0. 1 mg/kg, cognitive deficits were observed only after the onset of motor symptoms, but not prior to the onset of these symptoms; 0.2 mg / kg reserpine repeated treatment has jeopardized the cognitive assessment due to the presence of severe motor deficits. Thus, we suggest that the protocol of treatment with reserpine used in this work is a viable alternative for studies of the progressive appearance of parkinsonian signs in rats, especially concerning motor symptoms. As for the cognitive symptoms, we suggest that more studies are needed, possibly using other behavioral models, and / or changing the treatment regimen

Caracterização comportamental endócrina das fases ontogenéticas de sagüi comum (Callithrix jacchus)

The use of animal models in biomedical research is ever increasing. Models that use primates might also have advantages in terms of low maintenance costs and availability of biological knowledge, thereby favoring their use in different experimental protocols. Many current stress studies use animal models at different developmental stages since biological response differs during ontogeny. The aims of this study were to perform a detailed characterization of the developmental stages of common marmosets (Callithrix jacchus), a very important animal model used in biomedical research. Ten subjects, 6 females and 4 males, were followed from birth to initial adult age (16 months). Behavioral and fecal collection for measurement of adrenal (cortisol) and sex (progesterone, estradiol and androgens) hormones took place twice a week during the first month of life and once a week for the remainder of the study. Behavior was observed for 30 minutes in the morning (0700-09:00h) and afternoon (12:00-14:00h). Behavioral profile showed changes during ontogeny, characterizing the 4 developmental stages and the respective phases proposed by Leão et al (2009).. Differentiation of developmental stages was considered using the onset, end, change and stabilization of the behavioral profile parental care (weaning and carrying), ingestion (solid food), affiliation (social grooming) and autogrooming, agonism (scent marking and piloerection) and play behavior and endocrine profile. Infant weaning and carrying terminated within the infantile stage and the peak of solid food ingestion was recorded in the infantile III phase. Receiving grooming was recorded earlier than grooming performed by the infant and autogrooming. The first episode of scent marking was recorded in the 4th week and it was the least variable behavior, in terms of its onset, which, in almost all animals, was between the 5th and 7th week of life. Solitary play and play with the twin started around the 7th week and play with other members of the group started 8 weeks later. Sex hormone secretion started to differ from basal levels between the 21st and 23rd week of life, in males and females, suggesting that puberty occurs simultaneously in both sexes. Basal cortisol, even at an early age, was higher in females than in males. However, cortisol was not correlated with the juvenile stage, as expected, since this stage corresponds to the transition between infancy and adult age and most behaviors are intensified by this time. The behavioral and endocrine profile of subadult animals did not differ from that of the adults. These results provide more detailed parameters for the developmental process of C. jacchus and open new perspectives for the use of experimental approaches focused on the intermediate ontogenetic phases of this species

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

Déficits de memória induzidos por baixas doses de reserpina em ratos: possível relação com prejuízos no processamento emocional na Doença de Parkinson

We have recently verified that the monoamine depleting drug reserpine at doses that do not modify motor function - impairs memory in a rodent model of aversive discrimination. In this study, the effects of reserpine (0.1-0.5 mg/kg) on the performance of rats in object recognition, spatial working memory (spontaneous alternation) and emotional memory (contextual freezing conditioning) tasks were investigated. While object recognition and spontaneous alternation behavior were not affected by reserpine treatment, contextual fear conditioning was impaired. Together with previous studies, these results suggest that mild monoamine depletion would preferentially induce deficits in tasks involved with emotional contexts. Possible relationships with cognitive and emotional processing deficits in Parkinson disease are discussed

Caracterização do ritmo de atividade motora durante a puberdade em sagüis (Callithrix jacchus) sob condições semi-naturais

Most of ontogenetic studies on circadian timing system have been developed on infants, adults and elderly. The puberty has not been a stage of life few studied, except for researches in human adolescents, that presents phase delay in sleep-wake cycle. However, few studies have focused on the basis of this circadian change due to methodological difficulties. Thus, an animal model to study the sleep-wake cycle at puberty is essential. In the common marmoset, a social primate, the circadian activity periodicity stabilizes around 4 months (juvenile stage) and the 8h period component has a seasonal variation. Puberty stage of this species begins near the 8th month of age in males and near the 7th month in females with 7 months of duration. With the aim to characterize the circadian motor activity rhythm during puberty in marmosets (Callithrix jacchus) the motor activity was continuous registered by actiwatches in 6 animals between 5-12 months. Since the social factor influence the behavior of this specie, behavioral observations were realized in 30 minutes windows twice/week to a general evaluation of the influence social interactions dynamic across experiment. Determination of puberty onset was done by fecal progesterone and estrogens in females, and androgens in males. From the analysis of the multiple regression test was selected a model that evaluate age and seasonal variables effect on the activity rhythm according to the higher explanation coefficient. The total activity was the only parameter influenced by age. Moreover, the activity onset was the parameter more explained by the model, and the sunrise was the factor that most influenced it. After the puberty onset, 2 dyads advanced the activity onset. The activity total decreased in 1 dyad and increased in 2 dyads. This increase may be related to the birth of infants in these families. The motor activity circadian component stabilized later in 1 dyad, coinciding with the puberty onset of these animals, while bimodality, caused by the 8 h component, was modulated by seasonality. The agonistic behavior was not evaluated due to reduced number of events. There were changes across ages in affiliative behavior of contact in 1 dyad, grooming done in 1 animal and grooming received in 2 animals. Although there is evidence of puberty effect on the activity motor rhythm, the photoperiodic fluctuations influenced the rhythm. Therefore is not possible to affirm if the puberty modulate the activity rhythm in marmosets

Avaliação dos efeitos do biperideno, diazepam e neuropeptídeos S sobre a memória e a ansiedade na tarefa do labirinto em T elevado em camundongos

Anxiety is an emotional phenomenon, and normally it is interpreted as an adaptative behavior front to adversities. In its pathological form, anxiety can severely affect aspects related to the personal and professional life. Studies have shown a close relationship between anxiety disorders and aversive memory processing. Considering that the pharmacotherapy of anxiety disorders is still limited, innovative anxiolytic agents are needed. In this regard, neuropeptides systems are interesting therapeutic targets to the treatment of psychopathologies. Neuropeptide S (NPS), a 20-aminoacid peptide, is the endogenous ligand of a G-protein coupled receptor (NPSR), which has been reported to evoke hyperlocomotion, awakefull states, besides anxiolysis and memory improvements in rodents. This study aimed to investigate the effects of biperiden (BPR; an amnesic drug), diazepam (DZP; an anxiolytic drug) and NPS at three distinct times: pre-training, post-training, and pre-test, in order to assess anxiety and memory process in the same animal model. The elevated Tmaze (ETM) is an apparatus derived from the elevated plus-maze test, which consists of one enclosed and two open arms. The procedure is based on the avoidance of open spaces learned during training session, in which mice were exposed to the enclosed arm as many times as needed to stay 300 s. In the test session, memory is assessed by re-exposing the mouse to the enclosed arm and the latency to enter an open arm was recorded. When injected pre-training, BPR (1 mg/kg) impaired learning and memory processing; DZP (1 and 2 mg/kg) evoked anxiolysis, but only at the dose of 2 mg/kg impaired memory; and NPS 0.1 nmol induced anxiolysis without affecting memory. Post-training injection of DZP (2 mg/kg) or BPR (1 and 3 mg/kg) did not affect memory consolidation, while the post-trainning administration of NPS 1 nmol, but not 0.1 nmol, improved memory in mice. Indeed, pre-trainning administration of NPS 1 nmol did not prevent memory impairment elicited by BPR (2 mg/kg, injected before training). In the open field test, BPR 1 mg/kg and NPS 1 nmol induced hyperlocomotion in mice. In conclusion, the proposed ETM task is practical for the detection of the anxiolytic and amnesic effects of drugs. The anxiolytic and memory enhancement effects of NPS were detected in the ETM task, and reinforce the role of NPS system as an interesting therapeutic target to the treatment of anxiety disorders

Efeitos da estimulação ambiental sobre os aspectos motores, cognitivos e neuronais em um modelo farmacológico progressivo da doença de Parkinson

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Effect of a nanostructured dendrimer-naloxonazine complex on endogenous opioid peptides mu(1) receptor-mediated post-ictal antinociception

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Long-term high-fat diet-induced obesity decreases the cardiac leptin receptor without apparent lipotoxicity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Autologous transplantation of adult adipose derived stem cells into rabbit urethral wall

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Population parameters in Brazilian Thoroughbred

The information in this study has been provided by the Brazilian Association of Racehorse Breeders [Associação do Brasileira dos Criadores do Cavalo de Corrida (ABCCC)]. It can be found in the files on the CD-ROM developed by the ABCCC in 1999. A total of 5008 finishing time records related to 2545 winning horses that ran in the classical calendar on Brazilian hippodromes during 25 years (197498) were analysed. There were a total of 9949 horses on the relationship matrix. The variance components were estimated using the multiple-trait derivate-free restricted maximum likelihood (MTDFREML) program, for an animal model. Generation intervals were higher in the maternal side (10.91 years) than in the paternal one (10.41 years). The estimates for genetic permanent environmental and phenotypic variances and heritability were 0.291, 0.161, 3.486 and 0.08, respectively. The phenotypic standard deviation for time in races was 1.86729 s. Genetic time trend on Thoroughbred races in Brazil was small and could be accelerated if selection considered the trait time effectively. With respect to the animal's country of birth, the results show that there has been an intense participation of foreign animals in breeding Brazilian Thoroughbreds.