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Psychology & Neuroscience, Volume: 3, Número: 1, Publicado: 2010
  • The first forum on the neurobiology of stress Editorial For The Special Section

    Brandão, Marcus Lira
  • The hypothalamic-pituitary-adrenal axis in anxiety and panic Special Section On Neurobiology Of Stress

    Graeff, Frederico Guilherme; Zangrossi Junior, Hélio

    Resumo em Inglês:

    This review article focuses on the differential activation of the hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety and panic. The results of experimental studies that assayed adrenocorticotropic hormone, cortisol and prolactin show that real-life panic attacks as well as those induced by selective panicogenic agents, such as lactate and carbon dioxide, do not activate the HPA axis. Accordingly, experiments carried out in two animal models of panic, namely electrical stimulation of the dorsal periaqueductal gray matter of the rat and the escape from the open arm of the elevated T maze, have shown that in neither case stress hormones are increased in the plasma. Also in humans, reported results have shown that neither cortisol nor prolactin levels were increased following simulated public speaking, an experimental task that has been related to panic, in either healthy volunteers or patients with panic disorder diagnosis. Therefore, although the panic attack causes a major sympathetic stimulation, it has little effect on the HPA axis. In contrast, anticipatory or generalized anxiety activates both the HPA and the sympatho-adrenal axes.
  • Towards a translational model of panic attack Special Section On Neurobiology Of Stress

    Schenberg, Luiz Carlos

    Resumo em Inglês:

    About 20 years ago, Deakin and Graeff proposed that whereas generalized anxiety disorder is produced by the overactivity of 5-HT excitatory projections from dorsal raphe nucleus to the areas of prefrontal cortex and amygdala which process distal threat, panic attacks are a dysfunction of 5-HT inhibitory projections from dorsal raphe nucleus to the dorsal periaqueductal gray matter, thereby releasing the responses to proximal threat, innate fear or anoxia. Besides, they suggested that the decrease in 5-HT1A neurotransmission in the hippocampus results in learned helplessness and depression. Accordingly, the Deakin Graeff hypothesis provided a unified frame to the widespread use of 5-HT selective reuptake inhibitors in generalized anxiety, panic disorder and depression. Competitor hypotheses implicate panic attacks with the abnormal functioning of locus coeruleus, basolateral amygdala, dorsomedial hypothalamus or an as-yet-unknown suffocation alarm system. Conversely, cognitive psychologists suggest that panic attacks result from the catastrophic (cortical) interpretation of bodily symptoms. In any event, translational models of panic attack are expected to reproduce the main features of clinical panic, namely, the patient's higher sensitivity to both lactate and CO2, the drug specific sensitivity, the lack of stress hormone responses during panic attacks, the higher vulnerability of women and the high comorbidity with agoraphobia, major depression and childhood separation anxiety. Therefore, here we review the main steps in the experimental approach to anxiety disorders which are paving the route towards a translational model of panic attack.
  • Cannabinoids, anxiety, and the periaqueductal gray Special Section On Neurobiology Of Stress

    Saito, Viviane M; Moreira, Fabrício A

    Resumo em Inglês:

    The use of Cannabis sativa by humans dates back several thousand years, for both its psychotomimetic and potential medicinal properties. As scientific research methods developed, the cannabinoids present in this herb were characterized, as well as their complex interface with the human central nervous system, provided by the activation of specific receptors. The subsequent description of an endogenous cannabinoid system in the mammalian brain shifted the notion of cannabis as a recreational drug to a therapeutic alternative for psychiatric disorders. However, the neuroanatomical sites mediating its effects have remained uncertain. In the present paper, we review recent data suggesting that the midbrain periaqueductal gray may be a structure involved in the anxiolytic-like effects of cannabinoids.
  • Hormonal and cognitive factors associated with the exploratory behavior of rats submitted to repeated sessions of the elevated plus-maze Special Section On Neurobiology Of Stress

    Albrechet-Souza, Lucas; Brandão, Marcus L

    Resumo em Inglês:

    Naive rats submitted to the elevated plus-maze (EPM) display a characteristic increase in open arm exploration and reduced risk assessment behaviors (RABs) after the administration of anxiolytic drugs. Upon re-exposure to the maze, however, the traditional measures of the EPM become resistant to these drugs. This intriguing phenomenon was initially observed for the benzodiazepine chlordiazepoxide and referred as one-trial tolerance (OTT). In this review, we summarized hormonal, cognitive and neuroanatomical data obtained from rats submitted to the test/retest protocol in the EPM. The re-exposure to the EPM is characterized by more prominent RABs and a distinct Fos protein distribution in the brain, particularly in limbic structures involved with the cognitive aspects of fear, such as the ventral regions of the medial prefrontal cortex (mPFC) and amygdala. Interestingly, naive rats treated with midazolam had a significant decrease in the number of Fos-positive neurons in the anterior cingulate cortex, area 1 (Cg1), anterior and dorsal premammillary nuclei of hypothalamus. On the other hand, midazolam caused a significant decrease in the number of Fos-positive neurons in the mPFC, amygdala, dorsomedial nucleus of hypothalamus and raphe nuclei in maze-experienced rats. Cg1 was the only structure targeted by the benzodiazepine in both sessions. Systemically administered midazolam before test or retest sessions reduced the RABs and plasma corticosterone levels in rats submitted to both sessions. Similar behavioral results were obtained with intra-Cg1 infusions of midazolam. The results reviewed here support the view of the crucial role of the RABs in the development of the OTT and point to this mPFC area as an important locus for the anxiolytic-like action of benzodiazepines in rodents.
  • Prior exposure to stress delays extinction but does not modify reinstatement of nicotine-induced conditioned place preference Special Section On Neurobiology Of Stress

    Leão, Rodrigo M; Cruz, Fábio C; Planeta, Cleopatra S

    Resumo em Inglês:

    Studies in humans suggest that exposure to stress is related to relapse to tobacco use. The reinstatement of conditioned place preference (CPP) provides a simple, noninvasive and easy approach to investigate the mechanisms for drug relapse. The present study investigated whether repeated exposure to stress could change the extinction and reinstatement of nicotine-induced CPP. Adult male Wistar were exposed to restraint-stress for 2 hours/daily for 7 days, while the control-group was left undisturbed during this period. One day after the last stress session the CPP protocol was carried out. Nicotine produced a place preference to the compartment paired with its injections during conditioning (.16 mg/kg, s.c.; four drug sessions). Once established, nicotine place preference was extinguished by alternate exposure to each compartment after a saline injection (four exposures to each compartment). The animals that did not show extinction of CPP were submitted to two other extinction sessions. Following this extinction phase, the reinstatement of place conditioning was investigated following a priming injection of nicotine. Both control and stress groups showed reinstatement of CPP. The percentage of rats from the stress group that extinguished nicotine-CPP in the first and second test was lower as compared to the control group. In conclusion, stress delayed the extinction of the nicotine-induced CPP, but did not modify the reinstatement.
  • Role of nitric oxide in the periaqueductal gray in defensive behavior in mice: influence of prior local N-methyl-D-aspartate receptor activation and aversive condition Special Section On Neurobiology Of Stress

    Nunes-de-Souza, Ricardo Luiz; Miguel, Tarciso Tadeu; Gomes, Karina Santos; Fugimoto, Juliana Sayuri; Mendes-Gomes, Joyce; Amaral, Vanessa Cristiane Santana; Carvalho-Netto, Eduardo Ferreira de

    Resumo em Inglês:

    Glutamate N-methyl-D-aspartate (NMDA) receptor activation within the dorsal column of the periaqueductal gray (dPAG) leads to antinociceptive, autonomic, and behavioral responses characterized as the fear reaction. Activation of NMDA receptors in the brain increases nitric oxide (NO) synthesis, and NO has been proposed to be a mediator of the aversive action of glutamate. This paper reviews a series of studies investigating the effects of neuronal NO synthase (nNOS) inhibition in the dPAG of mice in different aversive conditions. nNOS inhibition by infusion of Nω-propyl-L-arginine (NPLA) prevents fear-like reactions (e.g., jumping, running, freezing) induced by NMDA receptor stimulation within the dPAG and produces anti-aversive effects when injected into the same midbrain site in mice confronted with a predator. Interestingly, nNOS inhibition within the dPAG does not change anxiety-like behavior in mice exposed to the elevated plus maze (EPM), but it reverses the effect of an anxiogenic dose of NMDA injected into the same site in animals subjected to the EPM. Altogether, the results support a role for glutamate NMDA receptors and NO in the dPAG in the regulation of defensive behaviors in mice. However, dPAG nitrergic modulation of anxiety-like behavior appears to depend on the magnitude of the aversive stimulus.
  • Effects of contextual fear conditioning and pentylenetetrazol on panic-like reactions induced by dorsal periaqueductal gray stimulation with N-methyl-D-aspartate Special Section On Neurobiology Of Stress

    Galvão, Bruno de Oliveira; Larrubia, Bruno Costa; Hommes, Wouter Jan; Cardenas, Luis Fernando; Cruz, Antonio Pedro de Mello; Landeira-Fernandez, Jesus

    Resumo em Inglês:

    Electrical or chemical stimulation of the dorsal periaqueductal gray (DPAG) has been accepted as an animal model of panic attacks. This study investigates the influence of anticipatory anxiety in the occurrence of panic-like behavior induced by N-methyl-D-aspartate (NMDA) microinjection into the DPAG of rats. Behavioral (i.e., contextual fear conditioning) and pharmacological (i.e., pentylenetetrazol) manipulations were employed as animal models of anticipatory anxiety. In the first experiment, animals exposed to contextual cues that had been previously associated with electric footshocks through contextual fear conditioning were less likely than non-conditioned control animals to display defensive reactions such as running and jumping in response to microinjection of NMDA (0.3 µl of 15.0 µg/µl) into the DPAG. In the second experiment, rats were injected intraperitoneally with the anxiogenic drug pentylenetetrazol (PTZ, 15 mg/kg) 5 minutes before receiving intra-DPAG microinfusion with the same dose of NMDA as in Experiment 1. Panic-related behaviors were registered in an experimental arena immediately after NMDA microinfusion. As compared with saline pre-treated animals, PTZ significantly attenuated NMDA-induced panic-like reactions. These results further demonstrate the usefulness of DPAG chemical stimulation as an animal model of panic attacks and suggest that behavioral and pharmacological activation of the brain mechanisms underlying anticipatory anxiety might exert an antipanic-like effect.
  • Interventions in the neonatal environment in rats and their relationship to behavior in adulthood and maternal behavior Plasticity And Neural Development

    Azevedo, Márcia Scherem de; Souza, Fabiana Leopoldo de; Donadio, Márcio Vinícius Fagundes; Lucion, Aldo Bolten; Giovenardi, Márcia

    Resumo em Inglês:

    The objective of this study was to assess the role of environmental/nest components and maternal behavior after several neonatal interventions on subsequent behavioral responses. Male Wistar rats were subjected to different neonatal interventions and were later evaluated for innate fear-like behavior in adulthood. The experimental groups included nonhandled (i.e., animals were not touched), handled (i.e., animals were separated from their mother, removed from the nest, and handled for 10 min/day), brief maternal separation (i.e., the mother was removed from the homecage for 10 min/day, and the pups remained in their cages without being touched), and tactile stimulation (i.e., the mother was removed from the homecage, and pups were stimulated with a brush for 10 min/day within the nest). The mother's behavior was recorded during the neonatal period, and the male pups were later tested in the open field as adults. The results revealed that only mothers whose pups were handled had an increase in the duration of licking behavior compared with the other groups. In the open field test, we observed decreased behavioral innate fear-like responses in male adults in the handled and brief separation groups compared with the others groups. Our results confirm that interventions during the neonatal period cause stable behavioral changes (decreased innate fear) in adulthood and that absent or excessive tactile stimulation appears to be an important factor. Both repeated disruption of the mother-infant relationship and withdrawal from the environment/nest are factors that exert profound effects on the development of the animals.
  • Normative data and construct validity of the Rey Auditory Verbal Learning Test in a Brazilian elderly population Clinical And Experimental Neuropsychology

    Fichman, Helenice Charchat; Dias, Luciana Brooking Teresa; Fernandes, Conceição Santos; Lourenço, Roberto; Caramelli, Paulo; Nitrini, Ricardo

    Resumo em Inglês:

    The Rey Auditory Verbal Learning Test (RAVLT) is an episodic memory test that is influenced by demographic variables, such as age, education, and gender. Classic word list learning has also been well documented to be an experimental cognitive paradigm that is very useful for the detection of Alzheimer's disease. The present study analyzed the performance of healthy elderly subjects on the RAVLT, describing the effects of age, education, and gender. To verify its construct validity, the RAVLT was compared with delayed recall and recognition scores on the Brief Cognitive Screening Battery (DR-BCSB). The sample comprised 183 cognitively healthy elderly subjects from outpatient care units of two university reference centers in Rio de Janeiro and São Paulo, Brazil. All participants were subjected to physical and neurological evaluation and neuropsychological assessment. Pearson's correlation and Student's t-test were used to investigate the influence of demographic variables on RAVLT performance. To verify convergent-type construct validity, a correlation between RAVLT and DR-BCSB scores was calculated. Significant correlations were found between age and ΣA1-A5 (r = -.383, p < .01), A5-A1 (r = -.054, p < .01), A7 (r = -.361, p < .01), and REC A (r = -.288, p < .01). Educational level correlated with ΣA1-A5 (r = .405, p < .01), A5-A1 (r = .184, p < .01), A7 (r = .334, p < .01), and REC A (r = .329, p < .01). No correlation was found between gender and RAVLT performance. A significant correlation was also found between RAVLT and DR-BCSB performance (r = .5, p < .01). These results revealed some normative data and convergent-type construct validity of the RAVLT for a Brazilian elderly population.
  • The Rey Auditory Verbal Learning Test: normative data for the Brazilian population and analysis of the influence of demographic variables Clinical And Experimental Neuropsychology

    Magalhães, Sabrina S; Hamdan, Amer C

    Resumo em Inglês:

    The Rey Auditory Verbal Learning Test (RAVLT) is an efficient neuropsychological instrument for testing episodic declarative memory. Performance on this test can be influenced by demographic and cultural variables. The objective of the present study was to analyze the influence of demographics variables, such as age, gender, and education, on RAVLT performance in young and elderly adults. A Portuguese version of the RAVLT was administered to 302 healthy participants. Subjects were from both genders, ranging in age from 17 to 85 years (mean 50.6 ± 15.9 years) and in education from 1 to 20 years (mean 11.3 ± 3.7 years). Participants were grouped by age: 17-34 years old, 34-49 years old, 50-64 years old, and 65-85 years old. Pearson's Correlation analysis showed a significant association between RAVLT performance and both age and education (p < .001), but not between RAVLT performance and gender. Two-way analysis of variance revealed significant effects of age on all RAVLT measurements and significant effects of years of education on all measurements, with the exception of recognition. The present data indicate that participant age and education significantly influence performance on the RAVLT.
  • Color Trails Test: a Brazilian normative sample Clinical And Experimental Neuropsychology

    Rabelo, Ivan Sant' Ana; Pacanaro, Sílvia Verônica; Rossetti, Milena de Oliveira; Leme, Irene F. Almeida de Sá; Castro, Nelimar Ribeiro de; Güntert, Camila Marchi; Miotto, Eliane Correa; Lucia, Mara Cristina Souza de

    Resumo em Inglês:

    The present study aims to evaluate psychometric data on the population of Brazil using of the Color Trails Test (CTT). The instrument was applied to 1,942 subjects who came from the north (1.4%), northeast (10.4%), midwest (7.7%), southeast (65.9%), and south (13.9%) regions of Brazil. Ages varied from 18 to 86 years (M = 40.03 years; DP = 16.02), with 386 males (19.9%) and 1,556 females (80.1%). Regarding schooling, 57 (3%) of participants were illiterate, 1.240 (64%) had primary education and 645 (33%) had a high school and/or superior diploma. The length of schooling ranged from 0 to 14 (M = 7.81, SD = 3.51) years. Good accuracy ratings were obtained using Spearman's coefficient on the main measures of the CTT, including time of execution form 1 (0.76) and form 2 (0.82). Regional variations showed that the northeast region had the worst results on the instrument. Males had better performance on the proposed task, with significant differences between age groups and the worst results for ages greater than 60 years. For both sexes, an increase in score was noticed with increasing age, and better performance was found with increasing levels of education. The present results suggest that the CTT can identify attentional disturbances with significant variations in the time of execution.
  • A cultural study on decision making: performance differences on the Iowa gambling task between selected groups of brazilians and americans Clinical And Experimental Neuropsychology

    Bakos, Daniela Schneider; Denburg, Natalie; Fonseca, Rochele Paz; Parente, Maria Alice de Mattos Pimenta

    Resumo em Inglês:

    This study compared the performance of selected groups of Brazilian and American individuals on the Iowa Gambling Task (IGT). The sample was composed of 70 Brazilian and American individuals of both genders, divided into two groups of young and older adults. The two groups of Brazilians were composed of 10 young adults, aged 25 to 41 years, and 25 older adults, aged 60 to 75 years. The two groups of Americans were composed of 10 young adults, aged 28 to 39 years, and 25 older adults, aged 60 to 76 years. A two-way analysis of variance revealed differences in performance between Brazilian and American participants, regardless of age group (country, p = .001; age group, p = .134; country vs. age group, p = .291). Analyses of variance using age group and country as main factors did not reveal any difference between the two national groups with regard to the learning achieved during the task (block, p < .001; age group, p = .063; country, p = .086). The results suggest that culture, represented by the country of origin, influences the performance of individuals on the IGT, demonstrating the importance of validating an instrument for each cultural group on which it is used.
  • Influence of aversive visual stimulation on attention, working memory, and anxiety in university students Clinical And Experimental Neuropsychology

    Giron, Paulo Ricardo; Almeida, Rosa Maria Martins de

    Resumo em Inglês:

    The present study investigated the influence of aversive visual stimulation on anxiety, working memory, and selective attention. The study was conducted with 366 participants of both sexes, divided into three groups: (i) no visual stimuli (n = 128), (ii) neutral visual stimuli (n = 114), and (iii) aversive visual stimuli (n = 124). Two DVD films, one containing aversive stimuli and one containing neutral stimuli, were used for the respective groups. Each visual stimulation had a duration of 1 minute and 22 seconds. After viewing the DVD, anxiety, working memory, and attention were assessed. Concomitant with the increase in anxiety were deficits in working memory and deficits in selective attention in the group that was exposed to the aversive scenes. No gender differences were observed. These results suggest that aversive visual stimuli increase anxiety and decrease attention and working memory performance in university students.
  • Construct validity of behavioral models of anxiety: where experimental psychopathology meets ecology and evolution Behavior/systems/cognition

    Maximino, Caio; Brito, Thiago Marques de; Gouveia Jr, Amauri

    Resumo em Inglês:

    In experimental psychopathology, construct validity is usually enhanced by addressing theories from other fields in its nomological network. In the field of anxiety research, this construct is related to antipredator behavior, conserved across phylogeny in its functions and neural basis, but not necessarily on its topography. Even though the relations between behavioral models of anxiety and statements from behavioral ecology and evolutionary biology are commonly made in anxiety research, these are rarely tested, at least explicitly. However, in order to increase construct validity in experimental anxiety, testing predictions from those theories is highly desirable. This article discusses these questions, suggesting a few ways in which behavioral ecological and evolutionary hypotheses of anxiety-like behavior may be tested.
  • Binding spatial location and stimulus identity in short-term memory Behavior/systems/cognition

    Caprio, Marina; Godoy, Juliana Pardo Moura Campos; Galera, Cesar

    Resumo em Inglês:

    In the working memory model, phonological and visuospatial information are stored by separate and independent systems. However, sometimes binding of visual and verbal information must occur. This study investigated whether these memory systems cooperate in the recall of spatial location of a stimulus defined by both types of information. Participants memorized the spatial locations in which name-and-face pairs were presented and either recalled the position of a test stimulus in which the two types of information were always present (Experiment 1) or recalled the position of a test stimulus that non-predictively contained either the visual or verbal information (Experiment 2). The results showed no cooperation between visuospatial and phonological systems when both types of information were present in the test stimulus. Rather, a clear preference for verbal information was found (Experiment 1). When the test stimulus contained only one type of information, recall based on both verbal and visual information was impaired (Experiment 2). These results suggest that visual and verbal information are not automatically integrated into memory and that storage capacity is smaller for integrated information than for isolated information.
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