Involvement of median raphe nucleus 5-HT1A receptors in the regulation of generalized anxiety-related defensive behaviours in rats

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

Social separation and diazepam withdrawal increase anxiety in the elevated plus-maze and serotonin turnover in the median raphe and hippocampus

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

Anxiety-induced antinociception in mice: effects of systemic and intra-amygdala administration of 8-OH-DPAT and midazolam

Rationale: Mice exhibit antinociception after a single experience in the elevated plus maze (EPM), an animal model of anxiety. Objective: This study investigated the mechanisms involved in this form of anxiety-induced antinociception. Methods: Nociception was evaluated by means of the writhing test in mice confined either to the open or enclosed arms of the EPM. The effects of systemic (naloxone, midazolam and 8-OH-DPAT) or intra-amygdala (8-OH-DPAT. NAN-190 and midazolam) drug infusions were investigated in mice previously treated i.p. with 0.6% acetic acid, an algic stimulus that induces abdominal contortions. The effects of these drugs on conventional measures of anxiety (% entries and % time in open arms) in a standard EPM test were also independently investigated. Results: Open-arm confinement resulted in a high-magnitude antinociception (minimum 85%, maximum 450%) compared with enclosed arm confinement. The opiate antagonist naloxone (1 mg/kg and 10 mg/kg) neither blocked this open arm-induced antinociception (OAIA) nor modified indices of anxiety in EPM. Administration of midazolam (0.5-2 mg/kg, s.c.) increased OAIA and produced antinociception in enclosed confined animals, as well as attenuating anxiety in the EPM. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.05-1 mg/kg, s.c.) had biphasic effects on OAIA, antagonising the response at the lowest dose and intensifying it at the highest dose. In addition, low doses of this agent reduced anxiety in the EPM. Although bilateral injections of 8-OH-DPAT (5.6 nmol/0.4 mu l) or NAN-190 (5.6 nmol and 10 nmol/0.4 mu l) into the amygdala did not alter OAIA, increased anxiety was observed in the EPM. In contrast, intra-amygdala administration of midazolam (10 nmol and 30 nmol/0.4 mu l) blocked both OAIA and anxiety. Conclusions: These results with systemic and intracerebral drug infusion suggest that 5-HT(1A) receptors localised in the amygdala are not involved in the pain inhibitory processes that are recruited during aversive situations. However, activation of these receptors does phasically increase anxiety. Although the intrinsic antinociceptive properties of systemically administered midazolam confounded interpretation of its effects on OAIA, intra-amygdala injections of this compound suggest that benzodiazepine receptors in this brain region modulate both the antinociceptive and behavioural (anxiety) responses to the EPM.

Evaluation of the elevated T-maze as an animal model of anxiety in the mouse

The elevated T-maze has been developed as an animal model of anxiety to generate both conditioned and unconditioned fears in the same rat. This study explores a version of the elevated T-maze fit for mice. Inhibitory (passive) avoidance-conditioned fear-is measured by recording the latency to leave the enclosed arm during three consecutive trials. One-way escape-unconditioned fear-is measured by recording the time to withdraw from open arms. The results showed that mice do not appear to acquire inhibitory avoidance in the standard T-maze, since their latencies to leave enclosed arm did not increase along trials. Nevertheless, the open arms seemed to be aversive for mice, because the latency to leave the enclosed arm after the first trial was lower in a T-maze with the three enclosed arms than in the standard elevated T-maze, In agreement, the exposure of mice to an elevated T-maze without shield, that reduces the perception of openness, increased significantly the latencies to leave the enclosed arm, However, the absence of the shield also increased the time taken to leave the open arms when compared to that recorded in standard T-maze. Systematic observation of behavioral items in the enclosed arm has shown that risk assessment behavior decreases along trials while freezing increases. In the open arms, freezing did not appear to influence the high latency to leave this compartment, since mice spend only about 8% of their time exhibiting this behavior, These results suggest that mice acquire inhibitory avoidance of the open arms by decreasing and increasing time in risk assessment and freezing, respectively, along three consecutive trials, However, one-way escape could not be characterized. Therefore, there are important differences between mice (present results) and rats (previously reported results) in the performance of behavioral tasks in the elevated T-maze. (C) 1999 Elsevier B.V.

5-HT2 receptor activation in the midbrain periaqueductal grey (PAG) reduces anxiety-like behaviour in mice

It is widely acknowledged that the indoleamine neurotransmitter serotonin (5-HT) plays a dual role in the regulation of anxiety, a role that in part depends upon neuroanatomical locus of action. Thus, whereas stimulation of 5-HT1A or 5-HT2 receptors in the limbic forebrain (amygdala, hippocampus) enhances anxiety-like responding in rodents, activation of corresponding receptor populations in the midbrain periaqueductal grey (PAG) more often than not reduce anxiety-like behaviour. The present study specifically concerns the anxiety-modulating influence of 5-HT2 receptors within the mouse PAG. Experiment 1 assessed the effects of intra-PAG infusions of the 5-HT2B/2C receptor agonist mCPP (0, 0.03, 0.1 or 0.3 nmol/0.1 mu l) on the behaviour of mice exposed to the elevated plus-maze. As mCPP acts preferentially at 5-HT2B and 5-HT2C receptors, Experiment 2 investigated its effects in animals pretreated with ketanserin, a preferential 5-HT2A/2C receptor antagonist. In both cases, test sessions were videotaped and subsequently, scored for anxiety-like behaviour (e.g., percentage of open arm entries and percentage of open arm time) as well as general locomotor activity (closed arm entries). The results of Experiment I showed that mCPP microinfusions (0.03 and 0.1 nmol) into the PAG of mice decreased behavioural indices of anxiety without significantly altering general activity measures. In Experiment 2, the anxiolytic-like profile of intra-PAG mCPP (0.03 nmol) was substantially attenuated by intra-PAG pretreatment with an intrinsically inactive dose of the preferential 5-HT2A/2C receptor antagonist, ketanserin (10 nmol/0.1 mu l). Together, these data suggest that 5HT(2C) receptor populations within the midbrain PAG play an inhibitory role in plus-maze anxiety in mice. (C) 2007 Elsevier B.V. All rights reserved.

Estresse entre professoras do ensino fundamental de escolas públicas estaduais

O artigo relata pesquisa que visou, entre outros objetivos, identificar a presença do estresse, a sintomatologia e as fases apresentadas pelos professores de 1ª a 4ª série do Ensino Fundamental atuantes em escolas públicas estaduais de uma cidade do Interior de São Paulo. Participaram do estudo 175 professores, perfazendo, aproximadamente, 70% dos profissionais de Ensino Básico I (PEB-I) em atuação no município. Para obtenção dos objetivos foram utilizados dois instrumentos de coleta de dados: o ISSL (Inventário de Sintomas de Estresse) e um questionário para caracterizar a população pesquisada. A pesquisa revelou que 56,6% dos professores estão experimentando estresse, cujos principais sintomas presentes são: sensação de desgaste físico constante, cansaço constante, tensão muscular, problemas com a memória, irritabilidade excessiva, cansaço excessivo, angústia/ansiedade diária, pensar constantemente em um só assunto e irritabilidade sem causa aparente.

Parametric analyses of anxiety in zebrafish scototaxis

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Interações físicas e psicossociais em mulheres com fibromialgia

Fibromyalgia (FM) is a non-inflammatory rheumatic syndrome of unknown etiology, with symptoms of diffuse musculoskeletal pain and presence of specific anatomic sites called tender points. The symptoms are often associated with fatigue, sleep disturbances, morning stiffness, alterations in pain perception, anxiety and depression. Fibromyalgia exhibits a correlation between physical and behavioral symptoms, which have a negative influence on the quality of life of patients. Emotional skills are important factors since they are related to subjective well-being, personal productivity, social interaction and interpersonal relationships. We aim to describe the physical and psychosocial interactions in women with FM, showing the association between perceived social support and affect with symptoms of pain, functionality and mood. We will also describe a body representation of pain in women with FM. Data were collected over 3 years and the sample size ranged between studies. This is an exploratory cross-sectional study conducted with a convenience sample of 63 women with FM and 42 healthy women as a control group (CT), aged 20-76 years, recruited through spontaneous demand at Onofre Lopes University Hospital (HUOL) and the Clinical School of Physiotherapy of Universidade Potiguar (UNP). The Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI), Social Support Scale (MOS), Hamilton Anxiety Scale and Scale of Positive and Negative Affect Schedule (PANAS), in addition to pressure algometry were used. For data analysis, we used parametric and non-parametric tests and a general linear model with adjustment variables and analysis of variance. A significant difference was found between pain threshold and tolerance, functionality, depression, anxiety, social support, and positive and negative affect between the groups. Affective states and social support were associated with anxiety, depression and functionality. A body was drawn representing pain with higher incidences in trapeze, supraspinatus and second ribs. The reason for studying sensory aspects, affective behavior and social support in FM patients opens perspectives for scientific and clinical research of this syndrome. Women with chronic pain such as FM appear to have altered mood states, less social support and affective dysfunctions, influencing the other symptoms of the syndrome

Estudos de validade da escala de dependência alcoólica do millon clinical multiaxial inventory iii para o Brasil

This study has as main objectives to translate and to adapt the MCMI-III to brazilian Portuguese, as well as investigate and analyze the involved modifications in the Alcohol Dependence Scale concerning to the results obtained on the validity and on the process of adaptation to Brazil. The inventory was translated and, posteriorly, applied on people with different reading levels to certify that the items are understandable to public in general, from diverse places of the country, divided into clinical and non-clinical groups. Were evaluated 2855 subjects between the ages of 18 and 85 years old, male and female, resident and dwellers of Brazilian cities. The application methods were face-to-face and computerized. Results showed that the clinical group presented significant differences between the means in comparison to the non-clinical group. Through the application of the General Health Questionnaire were developed studies related to the achievement of convergent validity and its results pointed to the relation between the instrument scores and the MCMI-III. The Alcohol Dependence Scale analysis indicated that people who reported abusive use of alcohol had highest scores, indicating adequacy of the instrument on identifying manifestation of disorders and syndromes. Nevertheless, further studies are necessary to the establishment of normative patterns to the Brazilian sample

H1 but not H2 histamine antagonist receptors mediate anxiety-related behaviors and emotional memory deficit in mice subjected to elevated plus-maze testing

This study investigated the role of H1 and H2 receptors in anxiety and the retrieval of emotional memory using a Trial 1/Trial 2 (T1/T2) protocol in an elevated plus-maze (EPM). Tests were performed on 2 consecutive days, designated T1 and T2. Before T1, the mice received intraperitoneal injections of saline (SAL), 20 mg/kg zolantidine (ZOL, an H2 receptor antagonist), or 8.0 or 16 mg/kg chlorpheniramine (CPA, an H1 receptor antagonist). After 40 min, they were subjected to the EPM test. In T2 (24 h later), each group was subdivided into two additional groups, and the animals from each group were re-injected with SAL or one of the drugs. In T1, the Student t-test showed no difference between the SAL and ZOL or 8 mg/kg CPA groups with respect to the percentages of open arm entries (%OAE) and open arm time (%OAT). However, administration of CPA at the highest dose of 16 mg/kg decreased %OAE and %OAT, but not locomotor activity, indicating anxiogenic-like behavior. Emotional memory, as revealed by a reduction in open arm exploration between the two trials, was observed in all experimental groups, indicating that ZOL and 8 mg/kg CPA did not affect emotional memory, whereas CPA at the highest dose affected acquisition and consolidation, but not retrieval of memory. Taken together, these results suggest that H1 receptor, but not H2, is implicated in anxiety-like behavior and in emotional memory acquisition and consolidation deficits in mice subjected to EPM testing.

EMOTIONAL BURDEN IN CAREGIEVERS of PATIENTS WITH OBSESSIVE-COMPULSIEVE DISORDER

The objective of this study was to evaluate the emotional burden, psychological morbidity, and level of family accommodation in caregivers of obsessive-compulsive disorder (OCD) patients, according to sociodemographic and clinical factors. Methods: Fifty Brazilian DSM-IV OCD patients and their caregivers were evaluated using the Family Accommodation Scale, the Zarit Burden Interview (ZBI), the Self-Report Questionnaire (caregivers), the Yale-Brown Obsessive-Compulsive Scale, and the Beck Depression Inventory (patients). Most caregivers (80%) were aged between 30 and 59 years and lived with the patient (88%). Results: Forty-two percent presented a common mental disorder and their mean ZBI score was 28.9. Family accommodation was moderate in 26% and severe or very severe in 24%. Caregivers' levels of psychological morbidity, accommodation, and emotional burden were associated with each other and with the severity of patient obsessive-compulsive and depressive symptoms. Conclusions: The results suggest that caregivers of OCD patients have important levels of burden and psychological morbidity and should receive orientation and support to minimize this emotional impact. Depression and Anxiety 25:1020-1027, 2008. (C) 2008 Wiley-Liss, Inc.

Effects of the essential oil from Citrus aurantium L. in experimental anxiety models in mice

Citrus aurantium L. is popularly used to treat anxiety, among other indications suggesting central nervous system action. Previous studies showed anxiolytic effect in the essential oil from peel in mice evaluated on the elevated plus maze [Carvalho-Freitas, M.I.R., Costa, M., 2002. Anxiolytic and sedative effects of extracts and essential oil from Citrus aurantium L. Biological and Pharmaceutical Bulletin 25, 1629-1633.]. In order to better characterize the activity of the essential oil, it was evaluated in two other experimental models: the light-dark box and the marble-burying test, respectively related to generalized anxiety disorder and to obsessive compulsive disorder. Mice were treated acutely by oral route 30 min (single dose) or once a day for 15 days (repeated doses) before experimental procedures. In light-dark box test, single treatment with essential oil augmented the time spent by mice in the light chamber and the number of transitions between the two compartments. There were no observed alterations in the parameters evaluated in light-dark box after repeated treatment. Otherwise, single and repeated treatments with essential oil were able to suppress marble-burying behavior. At effective doses in the behavioral tests, mice showed no impairment on rotarod procedure after both single and repeated treatments with essential oil, denoting absence of motor deficit. Results observed in marble-burying test, related to obsessive compulsive disorder, appear more consistent than those observed in light-dark box. (c) 2005 Elsevier B.V. All rights reserved.

Cerebellar Cognitive Affective Syndrome in Machado Joseph Disease: Core Clinical Features

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