Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas / Instigação social e confrontos agressivos repetidos em camundongos Swiss machos: análise de corticosterona plasmática e dos níveis de CRF e BDNF em áreas cerebrais límbicas

Abstract Introduction: Agonistic behaviors help to ensure survival, provide advantage in competition, and communicate social status. The resident-intruder paradigm, an animal model based on male intraspecific confrontations, can be an ethologically relevant tool to investigate the neurobiology of aggressive behavior. Objectives: To examine behavioral and neurobiological mechanisms of aggressive behavior in male Swiss mice exposed to repeated confrontations in the resident intruder paradigm. Methods: Behavioral analysis was performed in association with measurements of plasma corticosterone of mice repeatedly exposed to a potential rival nearby, but inaccessible (social instigation), or to 10 sessions of social instigation followed by direct aggressive encounters. Moreover, corticotropin-releasing factor (CRF) and brain-derived neurotrophic factor (BNDF) were measured in the brain of these animals. Control mice were exposed to neither social instigation nor aggressive confrontations. Results: Mice exposed to aggressive confrontations exhibited a similar pattern of species-typical aggressive and non-aggressive behaviors on the first and the last session. Moreover, in contrast to social instigation only, repeated aggressive confrontations promoted an increase in plasma corticosterone. After 10 aggressive confrontation sessions, mice presented a non-significant trend toward reducing hippocampal levels of CRF, which inversely correlated with plasma corticosterone levels. Conversely, repeated sessions of social instigation or aggressive confrontation did not alter BDNF concentrations at the prefrontal cortex and hippocampus. Conclusion: Exposure to repeated episodes of aggressive encounters did not promote habituation over time. Additionally, CRF seems to be involved in physiological responses to social stressors.

Resumo Introdução: Comportamentos agonísticos ajudam a garantir a sobrevivência, oferecem vantagem na competição e comunicam status social. O paradigma residente-intruso, modelo animal baseado em confrontos intraespecíficos entre machos, pode ser uma ferramenta etológica relevante para investigar a neurobiologia do comportamento agressivo. Objetivos: Analisar os mecanismos comportamentais e neurobiológicos do comportamento agressivo em camundongos Swiss machos expostos a confrontos repetidos no paradigma residente-intruso. Métodos: A análise comportamental foi realizada em associação com medidas de corticosterona plasmática em camundongos expostos repetidamente a um rival em potencial próximo, porém inacessível (instigação social), ou a 10 sessões de instigação social seguidas de encontros agressivos diretos. Além disso, o fator de liberação de corticotrofina (CRF) e o fator neurotrófico derivado do cérebro (BNDF) foram medidos no encéfalo desses animais. Camundongos controles não foram expostos à instigação social ou confrontos agressivos. Resultados: Os camundongos expostos a confrontos agressivos exibiram um padrão semelhante de comportamentos agressivos e não agressivos típicos da espécie na primeira e na última sessão. Em contraste com instigação social apenas, confrontos agressivos repetidos promoveram aumento na corticosterona plasmática. Após 10 sessões de confrontos agressivos, os camundongos apresentaram uma tendência não significativa de redução dos níveis de CRF no hipocampo, que se correlacionaram inversamente com os níveis plasmáticos de corticosterona. Por outro lado, sessões repetidas de instigação social ou confronto agressivo não alteraram as concentrações de BDNF no córtex pré-frontal e hipocampo. Conclusão: A exposição a episódios repetidos de encontros agressivos não promoveu habituação ao longo do tempo. Adicionalmente, o CRF parece estar envolvido nas respostas fisiológicas aos estressores sociais.

Problemas bioéticos en la investigación de nuevas vacunas: ¿obedecen a razones de salud pública? / Bioethical problems in researching new vaccines: Do they respond to public health reasons?

Los problemas éticos de las investigaciones sobre vacunas han crecido en las últimas décadas en frecuencia y magnitud debido a la posición dominante de la industria farmacéutica en el desarrollo de esos estudios. Las tradicionales cuestiones de seguridad y eficacia se han visto agravadas por el conflicto de intereses introducido por la competencia comercial en un mercado a escala global de miles de millones de dólares. La integridad profesional de los investigadores, la responsabilidad moral de los patrocinadores, y la regulación y control por parte de los Estados nacionales, se muestra cuestionada en varios ejemplos. Los resultados de estos cambios son las amenazas a la protección de los derechos de las personas incluidas en estas investigaciones y el discutible progreso que resulta para la salud pública.

The ethical problems in vaccine research have grown in frequency and magnitude in last decades, due to the dominant place of the pharmaceutical industry in the development of such studies. Traditional issues of security and efficacy have been aggravated by the conflicts of interests introduced by commercial competition in a global market worth billions of dollars. We present here a few examples in which the professional integrity of researchers, the moral responsibility of sponsors, and the public regulation and control by national States are put into question. The consequences of these changes represent serious threats to the rights of people included in these studies as well as disputable progress for public health.

Neurobehavioral assessment of appropriate for gestational and small for gestational age babies.

he present study was conducted to evaluate the neurobehaviour of term appropriate for gestational aland small for gestational age babies during the first two weeks of life in a tertiary care hospital. Forty eight appropriate and thirty small for gestation age babies were evaluated using Brazelton Neurobehavioural Assessment Scale on 3rd, 7th and 14th day of life. The behaviour of AGA babies is characterized by optimal performance in habituation, range of state, regulation of state and autonomic stability. The behavior is at low to mid-range in orientation and in motor clusters. All the behavior clusters showed improvement over first 14 days except for regulation of state which showed a lower performance on day 7 and 14. The behavior performance of SGA babies on day 3, compared to AGA babies, was lower in all the clusters except orientation where they performed much better. The percentage improvement of scores in SGA babies is higher than in AGA babies and by day 14 SGA babies are scoring higher than AGA babies in orientation, autonomic stability and regulation of state. The difference in the neurobehavior pattern of babies in relation to their intrauterine growth suggests need for appropriate care.

Long-term habituation (LTH) in the crab Chasmagnathus: a model for behavioral and mechanistic studies of memory

A decade of studies on long-term habituation (LTH) in the crab Chasmagnathus is reviewed. Upon sudden presentation of a passing object overhead, the crab reacts with an escape response that habituates promptly and for at least five days. LTH proved to be an instance of associative memory and showed context, stimulus frequency and circadian phase specificity. A strong training protocol (STP) (( 15 trials, intertrial interval (ITI) of 171 s) invariably yielded LTH, while a weak training protocol (WTP) (( 10 trials, ITI = 171 s) invariably failed. STP was used with a presumably amnestic agent and WTP with a presumably hypermnestic agent. Remarkably, systemic admministration of low doses was effective, which is likley to be due to the lack of an endothelial blood-brain barrier. LTH was blocked by inhibitors of protein and RNA synthesis, enhanced by protein kinase A (PKA) activators and reduced by PKA inhibitors, facilitated by angiotensin II and IV and disrupted by saralasin. The presence of angiotensins and related compounds in the crab brain was demonstrated. Diverse results suggest that LTH includes two components: an inital memory produced by spaced training and mainly expressed at an inital phase of testing, and a retraining memory produced by massed training and expressed at a later phase of testing (retraining). The inital memory would be associative, context specific and sensitive to cycloheximide, while the retraining memory would be nonassociative, context independent and insensitive to cycloheximide.

O estudo do fenômeno de habituaçäo em bêbes pré-termo de risco / Study the phenomenon of habituation in preterm infants

O presente trabalho teve por objetivo estudar a ocorrência do fenômeno de habituaçäo em bebês pré-termo atendidos na Unidade de Terapia Intensiva Neonatal do Hospital Säo Paulo/Escola Paulista de Medicina, pesquisando uma correlaçäo entre este fenômeno e um possível comprometimento neurológico. Para tanto, foram testados 18 bebês pré-termo, 9 do sexo feminino e 9 do sexo masculino, com idade gestacional variando de 27 a 36 6/7 semanas, sendo a testagem realizada em bebês de 5 dias a 9 meses de idade cronológica. O procedimento de testagem utilizado incluiu a observaçäo do comportamento auditivo frente a sons instrumentais de 70 a 100 dBNPS de intensidade e realizaçäo do teste de habituaçäo. Este teste constitui-se da repetiçäo dos estímulos sonoros frente a reaçäo de startle pela criança, num intervalo de 2 segundos entre cada repetiçäo, para observar-se a diminuiçäo ou desaparecimento desta reaçäo. O número máximo de apresentaçäo foi de 5 estímulos. Foi observada a presença do fenômeno de habituaçäo na 2ª repetiçao do estímulo em 10 crianças (55,5 por cento), na 3ª repetiçäo em 3 crianças (16,7 por cento) e na 4ª repetiçäo em 3 crianças (16,7 por cento). Observou-se ausência da habituaçäo em 2 crianças (11,1 por cento), as quais apresentaram exame neurológico alterado. Tais achados sugerem a existência de uma correlaçäo entre o fenômeno de habituaçäo e integridade do SNC. Diante destes resultados recomenda-se que a testagem do fenômeno de habituaçäo seja incluída nos procedimentos de avaliaçäo audiológica em bebês, visto que a ausência deste pode revelar indícios de alteraçöes do Sistema Nervoso Central

Effect of post-training injections of flumazenil into the amygdala, hippocampus and septum on retention of habituation and of inhibitory avoidance in rats

Adult rats were submitted to two different behavioral tasks using the same apparantus: the habituation of exploration of the apparatus considered as a novel environment as measured by the decrease in number of reaings and of ambulation between training and testing, and step-down inhibitory avoidance as measured by the increase in the latency to step down from a start platform into an electrified grid between the training and the test session.The training-test interval for both tasks was 20 h.The immediate post-training injection of the benzodiazepine receptor antagonist flumazenil (10 nmol) bilateral into the hippocampus enhanced retention of the two tasks.Application of the same drug, at the same dose to the septum or amygdala had no effect on habituation but enhanced retention of the avoidance task. The data are consistent with previous findings showing that both tasks are accompanied by the release of benzodiazepine like immunoreactivity in the three structures and that this release is greater after the avoidance task. The present findings suggest a differential regional involvement of endogenous benzodiazepine-mediated mechanisms in memory modulation, according to the task undertaken

Habituation to sound stimulation in detelencephalated pigeons (Columbia livia)

Habituation to sound stimulation was analyzed in terms of the functional role of the telencephalon in learning. Sixteen pigeons were exposed to 1000-Hz, 83-dB, 1-s sound (stimulus A) at 30-s intervals until there was habituation of the exploratory and pre-exploratory responses. The learning criterion was 10 trials without the occurrence of these responses. Twenty-four hours after habituation to stimulus A the birds were tested with a 500-Hz, 85-dB, 1-s sound (stimulus B). On the day following habituation to stimulus B, the birds of the experimental group (N=8) suffered ablation of the telencephalon and the birds of the control group (N=8) had sham surgery. Retesting with the same sequence of procedures was carried out 10 days after surgery. in the POST-lesion situation there was a decrease of the number of habituation trials to stimulus A (P<0.01) and to stimulus B (P<0.05) by experimental pigeons compared to the PRE-lesion situation. The data suggest an interaction of a facilitatory effect of the lesion and long-term learning effects

Single neuronal activities from CA3 region of hippocampus during conditioning, in mobile unanaesthetised conscious rabbits.

Single neuronal activities of 93 units from CA3 region of hippocampus were studied in unanaesthetised mobile rabbits. Effects of repeated reinforced conditioned stimuli (CS+) were observed on these neuronal firing pattern. The conditioned stimuli (CS) consisted of a tone 600 Hz for 6 seconds which was reinforced by a subcutaneous electrical shock (0.4 V, frequency 250 sec, and pulse width 300 microsec) for one second duration (CS+). Ten such CS+ were applied at the gap of 5 min, in between. As majority of CA3 neurons showed irregular spontaneous activities-the histograms drawn after calculation of interspike intervals showed a definite pattern of discharge which could be compared before, during and after multiple CS+. Two groups of neurons could be identified by their resting firing pattern. One group consisting of 21 neurons (22.5% approximately) showed complex spikes, with spike frequency less than 2 to 8 per sec. They were complex spike cells (CSC). The other group consisting of majority of neurons (72 neurons, 77.5% approximately) showed comparatively high spike frequency greater than 8 to 40 per sec (theta cells). Both the group of neurons reacted tonically to CS+. All complex spike cells and 54% of theta cells showed inhibitory reaction and 46% of theta cells showed excitatory reaction to CS+. But with repeated presentation (4th to 5th) of CS+ the reaction gradually declined and finally after tenth CS+ it disappeared and resting firing pattern was observed. Thus it seems that the neurons of CA3 region have an intrinsic habituation capability. The probable cause, mechanism and the significance for the habituation has been discussed here.