Blockade of fear-induced antinociception with intra-amygdala infusion of midazolam: Influence of prior test experience

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

Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

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

Ventrolateral periaqueductal gray lesion attenuates nociception but does not change anxiety-like indices or fear-induced antinociception in mice

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

Both alpha(1)- and beta(1)-adrenoceptors in the bed nucleus of the stria terminalis are involved in the expression of conditioned contextual fear

BACKGROUND AND PURPOSE The bed nucleus of the stria terminalis (BNST) is a limbic structure that is involved in the expression of conditioned contextual fear. Among the numerous neural inputs to the BNST, noradrenergic synaptic terminals are prominent and some evidence suggests an activation of this noradrenergic neurotransmission in the BNST during aversive situations. Here, we have investigated the involvement of the BNST noradrenergic system in the modulation of behavioural and autonomic responses induced by conditioned contextual fear in rats. EXPERIMENTAL APPROACH Male Wistar rats with cannulae bilaterally implanted into the BNST were submitted to a 10 min conditioning session (6 footshocks, 1.5 ma/ 3 s). Twenty-four hours later freezing and autonomic responses (mean arterial pressure, heart rate and cutaneous temperature) to the conditioning box were measured for 10 min. The adrenoceptor antagonists were administered 10 min before the re-exposure to the aversive context. KEY RESULTS L-propranolol, a non-selective beta-adrenoceptor antagonist, and phentolamine, a non-selective a-adrenoceptor antagonist, reduced both freezing and autonomic responses induced by aversive context. Similar results were observed with CGP20712, a selective beta 1-adrenoceptor antagonist, and WB4101, a selective a1-antagonist, but not with ICI118,551, a selective beta 2-adrenoceptor antagonist or RX821002, a selective a2-antagonist. CONCLUSIONS AND IMPLICATIONS These findings support the idea that noradrenergic neurotransmission in the BNST via a1- and beta 1-adrenoceptors is involved in the expression of conditioned contextual fear.

Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae)

The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA A antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA A receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA A receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.

The structure of psychopathological symptoms and the associations with DSM-diagnoses in treatment seeking individuals

BACKGROUND: Research on comorbidity of psychiatric disorders identifies broad superordinate dimensions as underlying structure of psychopathology. While a syndrome-level approach informs diagnostic systems, a symptom-level approach is more likely to represent the dimensional components within existing diagnostic categories. It may capture general emotional, cognitive or physiological processes as underlying liabilities of different disorders and thus further develop dimensional-spectrum models of psychopathology. METHODS: Exploratory and confirmatory factor analyses were used to examine the structure of psychopathological symptoms assessed with the Brief Symptom Inventory in two outpatient samples (n=3171), including several correlated-factors and bifactor models. The preferred models were correlated with DSM-diagnoses. RESULTS: A model containing eight correlated factors for depressed mood, phobic fear, aggression, suicidal ideation, nervous tension, somatic symptoms, information processing deficits, and interpersonal insecurity, as well a bifactor model fit the data best. Distinct patterns of correlations with DSM-diagnoses identified a) distress-related disorders, i.e., mood disorders, PTSD, and personality disorders, which were associated with all correlated factors as well as the underlying general distress factor; b) anxiety disorders with more specific patterns of correlations; and c) disorders defined by behavioural or somatic dysfunctions, which were characterised by non-significant or negative correlations with most factors. CONCLUSIONS: This study identified emotional, somatic, cognitive, and interpersonal components of psychopathology as transdiagnostic psychopathological liabilities. These components can contribute to a more accurate description and taxonomy of psychopathology, may serve as phenotypic constructs for further aetiological research, and can inform the development of tailored general and specific interventions to treat mental disorders.

Cross-culture perspectives on fear of HIV disease and AIDS in health care workers

Health care workers have been known to carry into the workplace a variety of judgmental and negative attitudes towards their patients. In no other area of patient care has this issue been more pronounced as in the management of patients with AIDS. Health care workers have refused to treat or manage patients with AIDS and have often treated them more harshly than identically described leukemia patients. Some health care institutions have simply refused to admit patients with AIDS and even recent applicants to medical colleges and schools of nursing have indicated a preference for schools in areas with low prevalence of HIV disease. Since the attitudes of health care workers do have significant consequences on patient management, this study was carried out to determine the differences in clinical practice in Nigeria and the United States of America as it relates to knowledge of a patient's HIV status, determine HIV prevalence and culture in each of the study sites and how they impact on infection control practices, determine the relationship between infection control practices and fear of AIDS, and also determine the predictors of safe infection control practices in each of the study sites.^ The study utilized the 38-item fear of AIDS scale and the measure of infection control questionnaire for its data. Questionnaires were administered to health care workers at the university teaching hospital sites of Houston, Texas and Calabar in Nigeria. Data was analyzed using a chi-square test, and where appropriate, a student t-tests to establish the demographic variables for each country. Factor analysis was done using principal components analysis followed by varimax rotation to simple structure. The subscale scores for each study site were compared using t-tests (separate variance estimates) and utilizing Bonferroni adjustments for number of tests. Finally, correlations were carried out between infection control procedures and fear of AIDS in each study site using Pearson-product moment correlation coefficients.^ The study revealed that there were five dimensions of the fear of AIDS in health care workers, namely fear of loss of control, fear of sex, fear of HIV infection through blood and illness, fear of death and medical interventions and fear of contact with out-groups. Fear of loss of control was the primary area of concern in the Nigerian health care workers whereas fear of HIV infection through blood and illness was the most important area of AIDS related feats in United States health care workers. The study also revealed that infection control precautions and practices in Nigeria were based more on normative and social pressures whereas it was based on knowledge of disease transmission, supervision and employee discipline in the United States, and thus stresses the need for focused educational programs in health care settings that emphasize universal precautions at all times and that are sensitive to the cultural nuances of that particular environment. ^

Mapping Emotion Terms into Affective Space: Further Evidence for a Four-Dimensional Structure

Recent empirical work on the semantics of emotion terms across many different cultures and languages, using a theoretical componential approach, suggested that four dimensions are needed to parsimoniously describe the semantic space of the emotion domain as reflected in emotion terms (Fontaine, Scherer, Roesch, & Ellsworth, 2007; Fontaine, Scherer, & Soriano, 2013). In addition to valence, power, and arousal, a novelty dimension was discovered that mostly differentiated surprise from other emotions. Here, we further explore the existence and nature of the fourth dimension in semantic emotion space using a much larger and much more representative set of emotion terms. A group of 156 participants each rated 10 out of a set of 80 French emotion terms with respect to semantic meaning. The meaning of an emotion term was evaluated with respect to 68 emotion features representing the appraisal, action tendency, bodily reaction, expression, and feeling components of the emotion process. A principal component analysis confirmed the four-dimensional valence, power, arousal, and novelty structure. Moreover, this larger and much more representative set of emotion terms revealed that the novelty dimension not only differentiates surprise terms from other emotion terms, but also identifies substantial variation within the fear and joy emotion families.

Fear of crime in Brisbane - Individual, social and neighbourhood factors in perspective

Numerous theories apply to fear of crime and each are associated with different kinds of variables. Most studies use only one theory, though this study examines the relative importance of different kinds of variables across a number of theories. The study uses data from a survey of residents in Brisbane, Australia to examine the relative importance of individual attributes, neighbourhood disorder, social processes and neighbourhood structure in predicting fear of crime. Individual attributes and neighbourhood disorder were found to be important predictors of fear of crime, while social processes and neighbourhood structure were found to be far less important. The theoretical implications are that the vulnerability hypothesis and the incivilities thesis are most appropriate for investigating fear of crime, though social disorganization theory does provide conceptual support for the incivilities thesis. Although social processes are less important in predicting fear of crime than neighbourhood incivilities, they are still integrally related to fear of crime: they explain how incivilities arise, they buffer against fear of crime, and they are affected by fear of crime.

Changes In Chromatin Structure In Nih 3t3 Cells Induced By Valproic Acid And Trichostatin A.

Valproic acid (VPA) and trichostatin A (TSA) are known histone deacetylase inhibitors (HDACIs) with epigenetic activity that affect chromatin supra-organization, nuclear architecture, and cellular proliferation, particularly in tumor cells. In this study, chromatin remodeling with effects extending to heterochromatic areas was investigated by image analysis in non-transformed NIH 3T3 cells treated for different periods with different doses of VPA and TSA under conditions that indicated no loss of cell viability. Image analysis revealed chromatin decondensation that affected not only euchromatin but also heterochromatin, concomitant with a decreased activity of histone deacetylases and a general increase in histone H3 acetylation. Heterochromatin protein 1-α (HP1-α), identified immunocytochemically, was depleted from the pericentromeric heterochromatin following exposure to both HDACIs. Drastic changes affecting cell proliferation and micronucleation but not alteration in CCND2 expression and in ratios of Bcl-2/Bax expression and cell death occurred following a 48-h exposure of the NIH 3T3 cells particularly in response to higher doses of VPA. Our results demonstrated that even low doses of VPA (0.05 mM) and TSA (10 ng/ml) treatments for 1 h can affect chromatin structure, including that of the heterochromatin areas, in non-transformed cells. HP1-α depletion, probably related to histone demethylation at H3K9me3, in addition to the effect of VPA and TSA on histone H3 acetylation, is induced on NIH 3T3 cells. Despite these facts, alterations in cell proliferation and micronucleation, possibly depending on mitotic spindle defects, require a longer exposure to higher doses of VPA and TSA.

Matrix Metalloproteinases And Left Ventricular Function And Structure In Spinal Cord Injured Subjects.

Subjects with spinal cord injury (SCI) exhibit impaired left ventricular (LV) diastolic function, which has been reported to be attenuated by regular physical activity. This study investigated the relationship between circulating matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) and echocardiographic parameters in SCI subjects and the role of physical activity in this regard. Forty-two men with SCI [19 sedentary (S-SCI) and 23 physically-active (PA-SCI)] were evaluated by clinical, anthropometric, laboratory, and echocardiographic analysis. Plasmatic pro-MMP-2, MMP-2, MMP-8, pro-MMP-9, MMP-9, TIMP-1 and TIMP-2 levels were determined by enzyme-linked immunosorbent assay and zymography. PA-SCI subjects presented lower pro-MMP-2 and pro-MMP-2/TIMP-2 levels and improved markers of LV diastolic function (lower E/Em and higher Em and E/A values) than S-SCI ones. Bivariate analysis showed that pro-MMP-2 correlated inversely with Em and directly with E/Em, while MMP-9 correlated directly with LV mass index and LV end-diastolic diameter in the whole sample. Following multiple regression analysis, pro-MMP-2, but not physical activity, remained associated with Em, while MMP-9 was associated with LV mass index in the whole sample. These findings suggest differing roles for MMPs in LV structure and function regulation and an interaction among pro-MMP-2, diastolic function and physical activity in SCI subjects.

Growth Factor Stimulation Improves The Structure And Properties Of Scaffold-free Engineered Auricular Cartilage Constructs.

The reconstruction of the external ear to correct congenital deformities or repair following trauma remains a significant challenge in reconstructive surgery. Previously, we have developed a novel approach to create scaffold-free, tissue engineering elastic cartilage constructs directly from a small population of donor cells. Although the developed constructs appeared to adopt the structural appearance of native auricular cartilage, the constructs displayed limited expression and poor localization of elastin. In the present study, the effect of growth factor supplementation (insulin, IGF-1, or TGF-β1) was investigated to stimulate elastogenesis as well as to improve overall tissue formation. Using rabbit auricular chondrocytes, bioreactor-cultivated constructs supplemented with either insulin or IGF-1 displayed increased deposition of cartilaginous ECM, improved mechanical properties, and thicknesses comparable to native auricular cartilage after 4 weeks of growth. Similarly, growth factor supplementation resulted in increased expression and improved localization of elastin, primarily restricted within the cartilaginous region of the tissue construct. Additional studies were conducted to determine whether scaffold-free engineered auricular cartilage constructs could be developed in the 3D shape of the external ear. Isolated auricular chondrocytes were grown in rapid-prototyped tissue culture molds with additional insulin or IGF-1 supplementation during bioreactor cultivation. Using this approach, the developed tissue constructs were flexible and had a 3D shape in very good agreement to the culture mold (average error <400 µm). While scaffold-free, engineered auricular cartilage constructs can be created with both the appropriate tissue structure and 3D shape of the external ear, future studies will be aimed assessing potential changes in construct shape and properties after subcutaneous implantation.

Ssr-based Genetic Diversity And Structure Of Garlic Accessions From Brazil.

Garlic is a spice and a medicinal plant; hence, there is an increasing interest in 'developing' new varieties with different culinary properties or with high content of nutraceutical compounds. Phenotypic traits and dominant molecular markers are predominantly used to evaluate the genetic diversity of garlic clones. However, 24 SSR markers (codominant) specific for garlic are available in the literature, fostering germplasm researches. In this study, we genotyped 130 garlic accessions from Brazil and abroad using 17 polymorphic SSR markers to assess the genetic diversity and structure. This is the first attempt to evaluate a large set of accessions maintained by Brazilian institutions. A high level of redundancy was detected in the collection (50 % of the accessions represented eight haplotypes). However, non-redundant accessions presented high genetic diversity. We detected on average five alleles per locus, Shannon index of 1.2, HO of 0.5, and HE of 0.6. A core collection was set with 17 accessions, covering 100 % of the alleles with minimum redundancy. Overall FST and D values indicate a strong genetic structure within accessions. Two major groups identified by both model-based (Bayesian approach) and hierarchical clustering (UPGMA dendrogram) techniques were coherent with the classification of accessions according to maturity time (growth cycle): early-late and midseason accessions. Assessing genetic diversity and structure of garlic collections is the first step towards an efficient management and conservation of accessions in genebanks, as well as to advance future genetic studies and improvement of garlic worldwide.

The Atomic Structure Of A Bare Buffer Layer On Sic(0001) Chemically Resolved.

A chemical-specific photoelectron diffraction structure determination of a carbon rich buffer layer on SiC is reported. In addition to the long-range ripple of this surface, a local buckling in the hexagonal sublattice, which breaks the local range order symmetry, was unraveled.

Crystal Structure Of (3e)-3-[(4-nitro-phen-oxy)-meth-yl]-4-phenyl-but-3-en-2-one.

In the title compound, C17H15NO4, the conformation about the C=C double bond [1.348 (2) Å] is E with the ketone group almost co-planar [C-C-C-C torsion angle = 7.2 (2)°] but the phenyl group twisted away [C-C-C-C = 160.93 (17)°]. The terminal aromatic rings are almost perpendicular to each other [dihedral angle = 81.61 (9)°] giving the mol-ecule an overall U-shape. The crystal packing feature benzene-C-H⋯O(ketone) contacts that lead to supra-molecular helical chains along the b axis. These are connected by π-π inter-actions between benzene and phenyl rings [inter-centroid distance = 3.6648 (14) Å], resulting in the formation of a supra-molecular layer in the bc plane.