A comparative study on the effects of the benzodiazepine midazolam and the dopamine agents, apomorphine and sulpiride, on rat behavior in the two-way avoidance test

In recent years. studies in behavioral pharmacology have shown the involvement of dopaminergic mechanisms in avoidance behavior as assessed by the two-way active avoidance test (CAR). Changes in dopaminergic transmission also occur in response to particularly threatening challenges. However, studies on the effects of benzodiazepine (BZD) drugs ill this test are still unclear. Given the interplay of dopamine and other neurotransmitters in the neurobiology of anxiety and schizophrenia the aim of this work was to evaluate the effects of systemic administration of midazolam, the dopaminergic agonist apomorphine, and the D(2) receptor antagonist sulpiride using the CAR, a test that shows good sensitivity to typical neuroleptic drugs. Whereas midazolam did not alter the avoidance response. apomorphine increased and sulpiride reduced them in this test. Escape was not affected by any drug treatments. Heightened avoidance was not associated with the increased motor activity caused by apomorphine. In contrast with the benzodiazepine midazolam, activation of post-synaptic D(2) receptors with apomorphine facilitates, whereas the D(2) receptor antagonism with sulpiride inhibited the acquisition of the avoidance behavior. Together, these results bring additional evidence for a role of D(2) mechanisms in the acquisition of the active avoidance. (C) 2009 Elsevier Inc. All rights reserved.

Sensing danger through the olfactory system: The role of the hypothalamic dorsal premammillary nucleus

The dorsal premammillary nucleus (PMd) has a critical role on the expression of defensive responses to predator odor. Anatomical evidence suggests that the PMd should also modulate memory processing through a projecting branch to the anterior thalamus. By using a pharmacological blockade of the PMd with the NMDA-receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5), we were able to confirm its role in the expression of unconditioned defensive responses, and further revealed that the nucleus is also involved in influencing associative mechanisms linking predatory threats to the related context. We have also tested whether olfactory fear conditioning, using coffee odor as CS, would be useful to model predator odor. Similar to cat odor, shock-paired coffee odor produced robust defensive behavior during exposure to the odor and to the associated context. Shock-paired coffee odor also up-regulated Fos expression in the PMd, and, as with cat odor, we showed that this nucleus is involved in the conditioned defensive responses to the shock-paired coffee odor and the contextual responses to the associated environment. (C) 2008 Elsevier Ltd. All rights reserved.

Expression of alpha-synuclein is increased in the hippocampus of rats with high levels of innate anxiety

A genomic region neighboring the alpha-synuclein gene, on rat chromosome 4, has been associated with anxiety- and alcohol-related behaviors in different rat strains. In this study, we have investigated potential molecular and physiological links between alpha-synuclein and the behavioral differences observed between Lewis (LEW) and Spontaneously Hypertensive (SHR) inbred rats, a genetic model of anxiety. As expected, LEW rats appeared more fearful than SHR rats in three anxiety models: open field, elevated plus maze and light/dark box. Moreover, LEW rats displayed a higher preference for alcohol and consumed higher quantities of alcohol than SHR rats. alpha-Synuclein mRNA and protein concentrations were higher in the hippocampus, but not the hypothalamus of LEW rats. This result inversely correlated with differences in dopamine turnover in the hippocampus of LEW and SHR rats, supporting the hypothesis that alpha-synuclein is important in the downregulation of dopamine neurotransmission. A novel single nucleotide polymorphism was identified in the 30-untranslated region (3`-UTR) of the alpha-synuclein cDNA between these two rat strains. Plasmid constructs based on the LEW 3`-UTR sequence displayed increased expression of a reporter gene in transiently transfected PC12 cells, in accordance with in-vivo findings, suggesting that this nucleotide exchange might participate in the differential expression of alpha-synuclein between LEW and SHR rats. These results are consistent with a novel role for alpha-synuclein in modulating rat anxiety- like behaviors, possibly through dopaminergic mechanisms. Since the behavioral and genetic differences between these two strains are the product of independent evolutionary histories, the possibility that polymorphisms in the alpha-synuclein gene may be associated with vulnerability to anxiety- related disorders in humans requires further investigation. Molecular Psychiatry (2009) 14, 894-905; doi: 10.1038/mp.2008.43; published online 22 April 2008

Hypothalamic sites responding to predator threats - the role of the dorsal premammillary nucleus in unconditioned and conditioned antipredatory defensive behavior

In this study we provide a comprehensive analysis of the hypothalamic activation pattern during exposure to a live predator or an environment previously associated with a predator. Our results support the view that hypothalamic processing of the actual and the contextual predatory threats share the same circuit, in which the dorsal premammillary nucleus (PMd) plays a pivotal role in amplifying this processing. To further understand the role of the PMd in the circuit organizing antipredatory defensive behaviors, we studied rats with cytotoxic PMd lesions during cat exposure and examined the pattern of behavioral responses as well as how PMd lesions affect the neuronal activation of the systems engaged in predator detection, in contextual memory formation and in defensive behavioral responses. Next, we investigated how pharmacological blockade of the PMd interferes with the conditioned behavioral responses to a context previously associated with a predator, and how this blockade affects the activation pattern of periaqueductal gray (PAG) sites likely to organize the conditioned behavioral responses to the predatory context. Behavioral observations indicate that the PMd interferes with both unconditioned and conditioned antipredatory defensive behavior. Moreover, we have shown that the PMd influences the activation of its major projecting targets, i.e. the ventral part of the anteromedial thalamic nucleus which is likely to influence mnemonic processing, and PAG sites involved in the expression of antipredatory unconditioned and conditioned behavioral responses. Of particular relevance, this work provides evidence to elucidate the basic organization of the neural circuits integrating unconditioned and contextual conditioned responses to predatory threats.

The indirect amygdala-dorsal striatum pathway mediates conditioned freezing: Insights on emotional memory networks

The dorsal striatum (DS) is involved in various forms of learning and memory such as procedural learning, habit learning, reward-association and emotional learning. We have previously reported that bilateral DS lesions disrupt tone fear conditioning (TFC), but not contextual fear conditioning (CFC) [Ferreira TL, Moreira KM, Ikeda DC, Bueno OFA, Oliveira MGM (2003) Effects of dorsal striatum lesions in tone fear conditioning and contextual fear conditioning. Brain Res 987:17-24]. To further elucidate the participation of DS in emotional learning, in the present study, we investigated the effects of bilateral pretest (postraining) electrolytic DS lesions on TFC. Given the well-acknowledged role of the amygdala in emotional learning, we also examined a possible cooperation between DS and the amygdala in TFC, by using asymmetrical electrolytic lesions, consisting of a unilateral lesion of the central amygdaloid nucleus (CeA) combined to a contralateral DS lesion. The results show that pre-test bilateral DS lesions disrupt TFC responses, suggesting that DS plays a role in the expression of TFC. More importantly, rats with asymmetrical pre-training lesions were impaired in TFC, but not in CFC tasks. This result was confirmed with muscimol asymmetrical microinjections in DS and CeA, which reversibly inactivate these structures. On the other hand, similar pretest lesions as well as unilateral electrolytic lesions of CeA and DS in the same hemisphere did not affect TFC. Possible anatomical substrates underlying the observed effects are proposed. Overall, the present results underscore that other routes, aside from the well-established CeA projections to the periaqueductal gray, may contribute to the acquisition/consolidation of the freezing response associated to a TFC task. It is suggested that CeA may presumably influence DS processing via a synaptic relay on dopaminergic neurons of the substantia nigra compacta and retrorubral nucleus. The present observations are also in line with other studies showing that TFC and CFC responses are mediated by different anatomical networks. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.

AMYGDALAR ROLES DURING EXPOSURE TO A LIVE PREDATOR AND TO A PREDATOR-ASSOCIATED CONTEXT

The amygdala plays a critical role in determining the emotional significance of sensory stimuli and the production of fear-related responses. Large amygdalar lesions have been shown to practically abolish innate defensiveness to a predator; however, it is not clear how the different amygdalar systems participate in the defensive response to a live predator. Our first aim was to provide a comprehensive analysis of the amygdalar activation pattern during exposure to a live cat and to a predator-associated context. Accordingly, exposure to a live predator up-regulated Fos expression in the medial amygdalar nucleus (MEA) and in the lateral and posterior basomedial nuclei, the former responding to predator-related pheromonal information and the latter two nuclei likely to integrate a wider array of predatory sensory information, ranging from olfactory to non-olfactory ones, such as visual and auditory sensory inputs. Next, we tested how the amygdalar nuclei most responsive to predator exposure (i.e. the medial, posterior basomedial and lateral amygdalar nuclei) and the central amygdalar nucleus (CEA) influence both unconditioned and contextual conditioned anti-predatory defensive behavior. Medial amygdalar nucleus lesions practically abolished defensive responses during cat exposure, whereas lesions of the posterior basomedial or lateral amygdalar nuclei reduced freezing and increased risk assessment displays (i.e. crouch sniff and stretch postures), a pattern of responses compatible with decreased defensiveness to predator stimuli. Moreover, the present findings suggest a role for the posterior basomedial and lateral amygdalar nuclei in the conditioning responses to a predator-related context. We have further shown that the CEA does not seem to be involved in either unconditioned or contextual conditioned anti-predatory responses. Overall, the present results help to clarify the amygdalar systems involved in processing predator-related sensory stimuli and how they influence the expression of unconditioned and contextual conditioned anti-predatory responses. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

The periaqueductal gray and its potential role in maternal behavior inhibition in response to predatory threats

Animals faced with conflicting cues, such as predatory threat and a given rewarding stimulus, must make rapid decisions to engage in defensive versus other appetitive behaviors. The brain mechanisms mediating such responses are poorly understood. However, the periaqueductal gray (PAG) seems particularly suitable for accomplishing this task. The PAG is thought to have, at least, two distinct general roles on the organization of motivated responses, i.e., one on the execution of defensive and reproductive behaviors, and the other on the motivational drive underlying adaptive responses. We have presently examined how the PAG would be involved in mediating the behavioral choice between mutually incompatible behaviors, such as reproduction or defense, when dams are exposed to pups and cat odor. First, we established the behavioral protocol and observed that lactating rats, simultaneously exposed to pups and cat odor, inhibited maternal behavior and expressed clear defensive responses. We have further revealed that cat odor exposure up-regulated Fos expression in the dorsal PAG, and that NMDA cytotoxic lesions therein were able to restore maternal responses, and, at the same time, block defensive responsiveness to cat odor. Potential paths mediating the dorsal PAG influences on the inhibition of appetitive (i.e., retrieving behavior) and consummatory (i.e., nursing) maternal responses are discussed. Overall, we were able to confirm the dual role of the PAG, where, in the present case, the dorsal PAG, apart from organizing defensive responses, also appears to account for the behavioral inhibition of non-defensive responses. (C) 2010 Elsevier B.V. All rights reserved.

Evidence for the thalamic targets of the medial hypothalamic defensive system mediating emotional memory to predatory threats

Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats. Anatomical findings suggest that the PMd is in a position to modulate memory processing through a projecting branch to specific thalamic nuclei, i.e., the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv). In the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual responses to predator-related cues) defensive behaviors. During cat exposure, all experimental groups exhibited intense defensive responses with the animals spending most of the time in the home cage displaying freezing behavior. However, during exposure to the environment previously associated with a cat, the animals with combined RE + AMv lesions, and to a lesser degree, animals with single AMv unilateral lesions, but not animals with single RE lesions, presented a reduction of contextual conditioned defensive responses. Overall, the present results provide clear evidence suggesting that the PMd`s main thalamic targets (i.e., the nucleus reuniens and the AMv) seem to be critically involved in the emotional memory processing related to predator cues. (C) 2010 Elsevier Inc. All rights reserved.

Dental anxiety and trait anxiety: an investigation of their relationship

Background Anxiety related to dental treatment is a fairly common phenomenon. Some studies have shown that there is an association between dental anxiety and general fears and anxiety, neuroticism and general psychological distress. Aim This study was designed to examine the relationship between dental anxiety and trait anxiety. Subjects and methods The sample consisted of 1,030 individuals (688 women; 342 men), aged 30.8 +/- 11.7 years. The Portuguese version of Corah`s Dental Anxiety Scale (DAS) and State-Trait Anxiety Inventory (STAI-T) were used. Results A statistically significant association between high DAS and high STAI-T, but not between high STAI-T and high DAS, was found. The data indicated that subjects with high dental anxiety tend to present with high trait anxiety, but high trait anxiety seems not to predispose to high dental anxiety. Conclusions Our results indicate that dental anxiety is specific, with its own features, and its development is not necessarily associated with trait anxiety.

Role of glutamate NMDA receptors and nitric oxide located within the periaqueductal gray on defensive behaviors in mice confronted by predator

The midbrain periaqueductal gray (PAG) is part of the brain system involved in active defense reactions to threatening stimuli. Glutamate N-methyl-d-aspartate (NMDA) receptor activation within the dorsal column of the PAG (dPAG) leads to autonomic and behavioral responses characterized as the fear reaction. Nitric oxide (NO) has been proposed to be a mediator of the aversive action of glutamate, since the activation of NMDA receptors in the brain increases NO synthesis. We investigated the effects of intra-dPAG infusions of NMDA on defensive behaviors in mice pretreated with a neuronal nitric oxide synthase (nNOS) inhibitor [N omega-propyl-l-arginine (NPLA)], in the same midbrain site, during a confrontation with a predator in the rat exposure test (RET). Male Swiss mice received intra-dPAG injections of NPLA (0.1 or 0.4 nmol/0.1 mu l), and 10 min later, they were infused with NMDA (0.04 nmol/0.1 mu l) into the dPAG. After 10 min, each mouse was placed in the RET. NMDA treatment enhanced avoidance behavior from the predator and markedly increased freezing behavior. These proaversive effects of NMDA were prevented by prior injection of NPLA. Furthermore, defensive behaviors (e.g., avoidance, risk assessment, freezing) were consistently reduced by the highest dose of NPLA alone, suggesting an intrinsic effect of nitric oxide on defensive behavior in mice exposed to the RET. These findings suggest a potential role of glutamate NMDA receptors and NO in the dPAG in the regulation of defensive behaviors in mice during a confrontation with a predator in the RET.

Stärkande omvårdnad : En litteraturstudie om förlossningsrädsla under graviditet och förlossning

Förlossningsrädsla utgör en speciell utmaning för mödrahälsovården och förlossningsvården.En konsekvens av rädslan är att kvinnor allt oftare kräver kejsarsnitt utan medicinsk indikation. Syftet med denna studie var att belysa faktorer som ligger till grund för förlossningsrädsla samt att ta reda på hur omvårdnadspersonal kan ge stärkande omvårdnad till denna sårbara grupp. Metoden var en systematisk litteraturstudie som omfattade fjorton vetenskapliga artiklar. Materialet till litteraturstudien identifierades via datoriserad och manuell sökning i databaser och tidsskrifter på Högskolan Dalarnas bibliotek samt sjukhus biblioteket på Falu Lasarett. Sökningen gjordes i databaserna ELIN@dalarna, Pub Med, Swe Med, Libris och Google sholar. Sökord som användes var: Fear of childbirth. Resultatet visade att rädslans innehåll och natur hänger samman med kvinnans personliga förutsättningar samt den sociala situation hon lever i. En slutsats blev att många kvinnor behöver hjälp för sin oro inför förlossningen och många har i högre grad än andra väntande kvinnor haft besvär med psykisk ohälsa. En viktig förutsättning för ett optimalt och professionellt bemötande av den förlossningsrädda kvinnan är ett gott samarbete mellan hela vårdkedjan, så alla har samma synsätt. Genom att alla säger samma saker skapas en trygghet.

Förlossningsrädda kvinnors erfarenheter av Aurorasamtal ett till två år efter förlossning

Bakgrund: Av alla gravida kvinnor räknas omkring 5 % lida av svår förlossningsrädsla. Kvinnor med förlossningsrädsla löper högre risk för komplikationer under och efter graviditeten. I Sverige läggs idag mycket resurser på Auroraverksamhet för att hjälpa kvinnor med förlossningsrädsla. Det saknas omfattande utvärdering av Auroraverksamheten. Syfte: Syftet med detta fördjupningsarbete var att undersöka upplevelse och effekt av Aurorasamtal inför förlossning samt upplevelse av den efterföljande förlossningen bland först- och omföderskor. Metod: Studien har en retrospektiv studiedesign där datainsamling skedde via en enkätundersökning. Datamaterialet sammanställdes därefter i SPSS. Resultat: Majoriteten av kvinnorna upplevde att samtalen hjälpte dem till en mer positiv förlossningsupplevelse. Fler förstföderskor än omföderskor önskade planerat kejsarsnitt när de kom till Auroramottagningen. De flesta kvinnor som önskade vaginal förlossning blev vaginalt förlösta. Över hälften av kvinnorna som deltog i studien var mindre rädda för förlossning 1 – 2 år efter förlossningen än de upplevde att de var innan Aurorasamtalet och förlossningen. Konklusion: Aurorasamtal förefaller ha störst betydelse för omföderskor och för de kvinnor som önskar vaginal förlossning.

Att vårda patienter i rättspsykiatrisk vård som uppvisar självskadebeteende : sjuksköterskors erfarenheter och upplevelser

Deliberate self harm as defined pathologically as well as socially is becoming an increasing phenomenon within forensic psychiatry. Nurses working with patients who have self harm behaviour and are confined to forensic psychiatry face different challenges which affect their feelings and attitudes in different ways, in their nursing practice. Purpose: To explore nurses’ experiences of caring for patients who suffer from deliberate self harm behaviour and are confined to forensic psychiatry. Method: Qualitative semi- structured interview s from eight nurses working within the forensic psychiatric clinic. Interviews were analysed by using a qualitative content analysis. Results: They worked strategically and emphasized the importance of teamwork, good communication and urged for the need to get necessary education, staff focused tutoring and patient focused therapy. Conclusion: Need for necessary education, patient focused therapy and staff focused tutor is needed to empower staff working with patients who are confined within forensic psychiatry and suffer from deliberate self harm behaviour.

The facial affective scale as a predictor for pain unpleasantness when children undergo immunizations.

Needle fear is a common problem in children undergoing immunization. To ensure that the individual child's needs are met during a painful procedure it would be beneficial to be able to predict whether there is a need for extra support. The self-reporting instrument facial affective scale (FAS) could have potential for this purpose. The aim of this study was to evaluate whether the FAS can predict pain unpleasantness in girls undergoing immunization. Girls, aged 11-12 years, reported their expected pain unpleasantness on the FAS at least two weeks before and then experienced pain unpleasantness immediately before each vaccination. The experienced pain unpleasantness during the vaccination was also reported immediately after each immunization. The level of anxiety was similarly assessed during each vaccination and supplemented with stress measures in relation to the procedure in order to assess and evaluate concurrent validity. The results show that the FAS is valid to predict pain unpleasantness in 11-12-year-old girls who undergo immunizations and that it has the potential to be a feasible instrument to identify children who are in need of extra support to cope with immunization. In conclusion, the FAS measurement can facilitate caring interventions.

PANA V : Evaluation of a Literacy Project

PANA V Evaluation of a Literacy ProjectSUMMARY AND CONCLUSIONSThis evaluation set out to explore the impact of the literacy work carried out through PANA V. It focussed on clarifying effects such as empowerment and poverty reduction in relation to the civil society. Two specific objectives were to evaluate the methodological approach and the didactic materials and to evaluate the sustainability of the project.Although the focus of the evaluation has been PANA V, the project has been evaluated in its context, as one in a series of five projects located in Rwanda ten years after the war and genocide. The conclusion will consider future plans in this field.The evaluator has striven to create a holistic picture of the effects of the project, although the given time for the evaluation was short. Only three weeks were spent in the field study and only ten days in the actual field. Although there were some organisational and logistic problems, as is common when carrying out a study like this in a poor country, many literacy sites were visited and quite many participators were interviewed. The overall impression from the study is overwhelmingly positive. So many people commit themselves in this task of teaching Rwandans reading, writing and numeracy. Despite harsh conditions learners strive to learn and group leaders devote themselves to the task. Many leaders on different levels try their very best to manage their difficult and demanding task. The main objective was to explore the impact of the project on poverty reduction, particularly on empowerment and strategies for everyday life. Women were to be regarded particularly. From the results it is clear that the project has a strong, positive impact both on poverty reduction and empowerment of marginalised groups. Among those who have benefited from the alphabetisation are mainly women. Unfortunately, when it comes to leaders in PANA, who may also be said to have benefited from the project, only a small minority is women. This is something that is recommended that it be reconsidered inside the organisation. As a majority of the targeted learners are women, and as the economic and social situation of women in Rwanda is generally weak, this is a question that I recommend the Pentesostal church and ADEPR to look particularly into. With many women being single breadwinners of their households, it is important that also women get access to positions that may bring benefits of different kind.It is also clear that the project has positive effects for the civil society. In the present situation in Rwanda, during the process of reconciliation and rapid progress, basic education for the poor majority is a democratic issue. In a country with a plethora of internet-cafés in the capital and a small minority that use cars and mobile-telephones to communicate nation-wide, it is of outmost importance that the majority acquires basic education, of which literacy is a central part. To strengthen the civil society in Rwanda literacy is important. One central issue is then that Rwanda develops toward becoming a country where literacy is used for the benefit of the citizens and it is a democratic issue that all citizens get an opportunity to participate. Crucial for this is that strong efforts are put into primary schools nation-wide. Literacy projects for adults, like PANA, may only complement these efforts, but they constitute important and necessary complements. Other relevant ways to promote literacy are campaigns in Radio and TV and through cultural events such as festivals, music and theatre. News papers, magazines and books are natural parts of such campaigns as well as adult education. As stated under the results not much can be said about the didactics in this evaluation. On the whole the methodology and the materials fill their function well and receive a high reputation. As people learn to read and write under very simple conditions, obviously the approach is appropriate. A few suggestions may be given from the study:•Focus groups leaders’ attention on clearness, that they show very clearly what is to be read. Good structuring is probably of great importance for many learners.•Make clear what is tested in the tests and consider the possibility to use a holistic test that would be more congruent with the methodology. The possibility to use only one grade, pass, would enable a more practical test, such as reading a short, relevant text, writing something relevant and solving practical mathematic problems. Avoid tests that demand school knowledge.•Avoid using methaphors such as “fight against illiteracy” and connections between illiteracy/literacy and darkness/light. It is not true that illiteracy causes bad things and that literacy only brings good. •Be prepared that it may be more difficult in the future to achieve the goals as it may be the case that the early learners where the ones who achieved easily. The goal of “literacy in six month” in PANA will probably hold only for some learners but also those who do not manage in six months need literacy skills.A third objective was to secure sustainability. As for sustainability of the project in itself, and of the literacy process, the main conclusion is that there is a good potential. The commitment and devotedness among many involved in PANA proves good. One weakness is individual leaders in ADEPR who do not see this as an important task for the Pentecostal church in Rwanda. Other weaknesses are the unwillingness to mention explicitly the wish, for example among group leaders, to get some kind of incentive and the fear of loosing believers by cooperation with other organisations. A higher degree of transparency in this issue would probably solve some irritations and tensions.As for the sustainability of the literacy skills much may be done to improve. The acquired skills seem to be comparably relevant. The level achieved, and the level tested, may be defined as basic literacy skills, consisting of basic reading, writing and numeracy skills. However, these skills are very restricted and there is a high risk that the skills will decline, which means that there is a high risk that people will forget how to read and write because of lack of exercising. From these conclusions a few suggestions for future development will be given.