Lesões na parte ventral do núcleo anteromedial do tálamo (AMv) interferem no processamento da memória aversiva predatória sem no entanto influenciar as respostas de defesa inatas do animal frente a um predador. O escopo deste trabalho foi entender melhor o papel do AMv e investigar se seus alvos de projeção corticais também interferem no processamento da memória aversiva. No primeiro experimento detectamos que o AMv participa da aquisição da memória aversiva. As áreas corticais pré-límbica, cingulada anterior, visual anteromedial e retroesplenial ventral, recebem e integram entre si projeções oriundas do AMv, além de enviar projeções para a amígdala e hipocampo. Estas áreas corticais estão seletivamente recrutadas durante a exposição ao predador, e observamos que lesões neuroquímicas afetaram severamente a formação da memória aversiva. Nossos dados sugerem que há um circuito de áreas corticais que está criticamente envolvido no processo mnemônico aqui abordado, e fornece as primeiras evidências para a hipótese de módulos corticais a partir do conectoma do rato. / Neurochemical lesions placed into ventral part of anteromedial thalamic nucleus (AMv) disrupt contextual, but not innate, fear responses to predatory threats. In the present investigation, we determined whether the AMv is involved in the acquisition and/or retrieval of the conditioned responses, and if its cortical targets are involved in the fear memory processing. In the first assay, we found that AMv has a critical role in the acquisition of conditioned responses. The cortical areas prelimbic (PL), anterior cingulate area (ACA), anteromedial visual area (VISam) and the ventral part of retrosplenial area (RSPv), receive projections from AMv and are recruited during predator exposure. The integrity of these cortical areas is required for the processing of the mnemonic processes here addressed. Our data corroborate current ideas on functional cortical modules, and help to elucidate how they are involved in the acquisition of fear memories related to life threatening situations.

[pt] A matéria cinzenta periaquedutal dorsal (MCPD) é associada com comportamento defensivo e ataques de pânico em humanos. Estimulações elétricas ou farmacológicas da MCPD induzem a reações aversivas de corrida e pulo em ratos. Os resultados no experimento 1 indicaram que animais submetidos a um contexto previamente associado com choques nas patas, obtiveram um comportamento defensivo de congelamento robusto e tiveram menores reações defensivas de corridas e pulos através da microinjeção de de 0.3 µl N-metil-D- aspartato (NMDA; 15.0 mg/kg), quando comparado com o grupo controle que não foi exposto ao procedimento de medo ao contexto. No experimento 2, o efeito de injeções de pentilenotetrazol (PTZ; 15.0 mg/kg i.p.) em ratos microinjetados com NMDA nas reações de corridas e pulos foi investigado. Os resultados mostraram que o PTZ (1ml/100gr) foi capaz de minimizar as reações aversivas de corridas e pulos induzidas pela microinjeção de NMDA na MCPD. Esses resultados sugerem que a ativação de mecanismos cerebrais que permeiam a ansiedade produzem um efeito inibitório em ataques de pânico. / [en] The dorsal portion of the periaqueductal gray (DPAG) is notably associated with defensive behavior and panic attacks in humans. Electrical or pharmacological stimulation of the DPAG induces aversive reactions such as running and jumping in rats. Our results indicate that animals exposed to contextual cues, that were previously associated with electrical footshocks, engaged in robust defensive freezing behavior and were less likely to display running and jumping defensive reactions by microinjection of 0.3 µl N-methyl-D-aspartate (NMDA; 15.0 mg/kg) into DPAG when compared with control animals that were not exposed to the context fear conditioning procedure. Furthermore the effect of pentylenotetrazole injections (PTZ; 15.0 mg/kg i.p.) in microinjected NMDA rats in aversive reactions of running and jumping was investigated. The result showed that PTZ dose (1ml/100gr) was capable to minimize the aversive reactions of running and jumping induced by microinjection of NMDA into DPAG. These results suggest that activation of the brain mechanisms that underlie anxiety produces an inhibitory effect on panic attacks.

Etologicamente, os animais expressam repostas de medo frente a um predador ou a um co-especifico e a organização neural de respostas defensivas intraespecíficas são pouco conhecidas. Assim, o objetivo deste trabalho foi estudar o papel hipotalâmico na organização da defesa intraespecífica. Observamos que o núcleo pré-mamilar dorsal do hipotálamo também está ativo durante nesse tipo de defesa, porém porções distintas do mesmo. A lesão desse núcleo em ratos expostos a derrota social levou a importantes alterações comportamentais, praticamente abolindo comportamentos de defesa passiva. Notamos que regiões do hipotálamo lateral são as principais projeções aferentes do núcleo pré-mamilar dorsal e o principal alvo eferente é a coluna dorsomedial da matéria cinzenta periaquedutal. Concluímos que o hipotálamo é fundamental para a organização da defesa intraespecífica e que comportamentos defensivos inter e intra-específicos se utilizam de caminhos neurais distintos. / In nature, animals express fear responses toward a predator or a co-specific and not much is known about the neural organization of intra-specific defense. Therefore, the aim of this work was to analyze the role that the hypothalamus plays during the intra-specific defense expression. We observed that the dorsal premammilary nucleus is also mobilized during the agonistic encounter, but a different portion. Dorsal premammilary nucleus lesioned intruders led to important defense alterations, almost abolishing passive forms of defensive behavior. Notably, regions in lateral hypothalamus are particularly important for activating the dorsal premammilary nucleus and its efferent projection to the dorsomedial column of periaqueductal gray matter is the most important outcome for the defensive behavior expression. Concluding, the hypothalamus is fundamental for the neural organization of intra-specific defense and inter and intra-specific defensive behaviors are organized by distinct neural pathways.

Primeiramente, investigamos as respostas defensivas de animais lesionados da parte dorsal da PAG rostral durante o confronto predatório. Estes animais permaneciam com as respostas de avaliação de risco (AR) porem perdem as respostas de freezing. Em um segundo estudo, analisamos as respostas defensivas frente ao predador em animais lesionados da parte ventrolateral da PAG caudal. Estes animais perdem as respostas de freezing e aumentam as respostas de AR. Será que as respostas de AR dependem da integridade da parte dorsal rostral e ventrolateral caudal da PAG ? Por último, investigamos as respostas defensivas em animais com lesão combinada destas áreas. Observamos uma diminuição drástica das AR e um aumento das respostas exploratórias. Provavelmente, as respostas de AR estão sendo moduladas pela parte dorsal rostral e ventrolateral caudal da PAG através de seus alvos ascendentes hipotalâmicos, e estes com o septo lateral. As respostas de freezing parecem ser moduladas por projeções descendentes da PAG para a medula espinal. / First, we investigated the defensive responses of injured animals of the dorsal part of the rostral PAG during predatory confrontation. These animals remained with the risk assessment responses (AR) however lose the freezing of response. In a second study, we analyzed the defensive responses front predator injured animals in the ventrolateral part of the caudal PAG. These animals lose the responses of freezing and increase AR responses. Does the AR responses depend on the integrity of dorsal part rostral and caudal ventrolateral PAG? Finally, we investigated the defensive responses in animals with combined injury of these areas. We observed a dramatic decrease of AR and an increase in exploratory response. Probably AR responses are modulated by the dorsal part of the rostral and caudal ventrolateral PAG through its hypothalamic ascendant targets, and these with the lateral septum. Freezing responses appear to be modulated by descending projections from the PAG to the spinal cord.

Etologicamente, os animais expressam repostas de medo frente a um predador ou a um co-especifico e a organização neural de respostas defensivas intraespecíficas são pouco conhecidas. Assim, o objetivo deste trabalho foi estudar o papel hipotalâmico na organização da defesa intraespecífica. Observamos que o núcleo pré-mamilar dorsal do hipotálamo também está ativo durante nesse tipo de defesa, porém porções distintas do mesmo. A lesão desse núcleo em ratos expostos a derrota social levou a importantes alterações comportamentais, praticamente abolindo comportamentos de defesa passiva. Notamos que regiões do hipotálamo lateral são as principais projeções aferentes do núcleo pré-mamilar dorsal e o principal alvo eferente é a coluna dorsomedial da matéria cinzenta periaquedutal. Concluímos que o hipotálamo é fundamental para a organização da defesa intraespecífica e que comportamentos defensivos inter e intra-específicos se utilizam de caminhos neurais distintos. / In nature, animals express fear responses toward a predator or a co-specific and not much is known about the neural organization of intra-specific defense. Therefore, the aim of this work was to analyze the role that the hypothalamus plays during the intra-specific defense expression. We observed that the dorsal premammilary nucleus is also mobilized during the agonistic encounter, but a different portion. Dorsal premammilary nucleus lesioned intruders led to important defense alterations, almost abolishing passive forms of defensive behavior. Notably, regions in lateral hypothalamus are particularly important for activating the dorsal premammilary nucleus and its efferent projection to the dorsomedial column of periaqueductal gray matter is the most important outcome for the defensive behavior expression. Concluding, the hypothalamus is fundamental for the neural organization of intra-specific defense and inter and intra-specific defensive behaviors are organized by distinct neural pathways.

Primeiramente, investigamos as respostas defensivas de animais lesionados da parte dorsal da PAG rostral durante o confronto predatório. Estes animais permaneciam com as respostas de avaliação de risco (AR) porem perdem as respostas de freezing. Em um segundo estudo, analisamos as respostas defensivas frente ao predador em animais lesionados da parte ventrolateral da PAG caudal. Estes animais perdem as respostas de freezing e aumentam as respostas de AR. Será que as respostas de AR dependem da integridade da parte dorsal rostral e ventrolateral caudal da PAG ? Por último, investigamos as respostas defensivas em animais com lesão combinada destas áreas. Observamos uma diminuição drástica das AR e um aumento das respostas exploratórias. Provavelmente, as respostas de AR estão sendo moduladas pela parte dorsal rostral e ventrolateral caudal da PAG através de seus alvos ascendentes hipotalâmicos, e estes com o septo lateral. As respostas de freezing parecem ser moduladas por projeções descendentes da PAG para a medula espinal. / First, we investigated the defensive responses of injured animals of the dorsal part of the rostral PAG during predatory confrontation. These animals remained with the risk assessment responses (AR) however lose the freezing of response. In a second study, we analyzed the defensive responses front predator injured animals in the ventrolateral part of the caudal PAG. These animals lose the responses of freezing and increase AR responses. Does the AR responses depend on the integrity of dorsal part rostral and caudal ventrolateral PAG? Finally, we investigated the defensive responses in animals with combined injury of these areas. We observed a dramatic decrease of AR and an increase in exploratory response. Probably AR responses are modulated by the dorsal part of the rostral and caudal ventrolateral PAG through its hypothalamic ascendant targets, and these with the lateral septum. Freezing responses appear to be modulated by descending projections from the PAG to the spinal cord.

我國警察的任務，依警察法第二條規定為「依法維持公共秩序，保護社會安全，防止一切危害，促進人民福利。」致警察工作包羅萬象，使得警察人員成為政府推動許多行政事務的重要執行者，扮演政府與民眾之間的橋樑角色，是民眾接觸最頻繁的公務員；又因警察任務具有執法及管制的特性，影響民眾權益甚大，所以平時爭議頗多，其中尤以負責將警察任務轉化為實際行動的警察勤務基本單位的警勤區警員，更是警察組織對外的代表，其經常決定了警察政策的實際效果，所做所為不僅是民眾對警察組織評價的重要依據，更可能轉移至對政府的印象，故選擇其為本文的研究對象。 Lipsky(1980)的「第一線人員執行理論」(Theory of the work of street-level bureaucracies)，從第一線執行人員的工作本質，其身處的工作情境談到第一線執行人員的行為類型，本文即是以Lipsky之第一線執行理論為基礎架構，防禦行為（defensive behaviors）部分並參考Sorg(1983)的「基層官僚執行行為類型」及Ashforth和Lee(1990)的「防禦行為之初探模式」等研究，以實證調查方式，研究我國警勤區警員的防禦行為，目的在瞭解我國警勤區警員的工作環境及其適應環境的心態與方法；我國警勤區警員防禦行為的現況；他們為何會有這些行為表現？及不同防禦行為之重要決定因素。 為求能了解警勤區警員防禦行為之實際情形，恐態度認知和行為表現間存有差距，本研究嘗試結合質與量的研究方法，除對警勤區警員編製問卷施測外，亦由警察大學二年級至派出所實習的學生擔任觀察者，樣本之選取，係以立意抽樣法(purposive sampling)，配合觀察者之實習，選擇警察大學正科六十一期學生83年度實習派出(分駐)所內之所有警勤區員警為施測對象。研究編製「我國警勤區員警執勤模式問卷量表」，由員警填答，另設計「學生實習觀察問卷表」，由學生實習畢填寫，問卷調查資料，則進行次數(Frequency)、量表的效信度(Reliability & Validity)及因素分析(Factor Analysis)、描述性統計(Descriptive statistics)、卡方考驗(X2)、相關係數(Correlation Coefficient)、T考驗(T Test)、變異數分析(ANOVA)、迴歸分析(Regression Analysis)、逐步迴歸(Stepwise regression)、路徑分析(Path Analysis)、集群分析(Cluster Analysis)、區別分析(Discriminant analysis)等統計法分析。 研究發現摘錄如下： 一、我國警勤區警員防禦行為之現況：我國警勤區員警普遍存在「推諉責任」、「輕忽民眾」、「抑制變遷」等防禦行為，現況經分析員警和學生二組之調查結果，在「推諉責任」、「輕忽民眾」項，員警自認不會推諉責任及輕忽民眾需求（平均數低於中位數），但學生組的觀察，員警們有推諉責任及輕忽民眾需求的防禦行為（平均數則高於中位數），且二組間的差異經T檢定，達顯著水準；至於在「抑制變遷」因素項，二組的平均數皆高於中位數，員警的平均數高於學生組的平均數，表示警勤區警員對新政策、新措施在態度上是抗拒的，但學生們旁觀者的觀察，警勤區警員在行為表現上卻未如是強烈，研究者認為是「警察管理階層與執行階層鴻溝」與「警察服從天性」二者矛盾交織而成的現象：任何新的措施與作法皆會增加員警有形(工作量) 無形(心理層面)的負擔，員警在心態上是抗拒排斥改變的，但為因應組織監督考核的現況，故在行為上則是配合的。 經集群分析：「消極應付」組有618人為最高，「高度防禦」組607人，「積極認事」組則有448人，顯示有33.5%的勤區員警是以消極、應付的心態及行為模式在執行日常的勤務，有33%的警勤區警員會表現出積極的防禦行為，故有66.3%的警勤區員警有防禦行為。 二、警勤區員警處於民眾矛盾對待嚴重、各種內外環境交錯複雜之混沌環境中，同時法令不完備、工作單調矛盾具危險性常須處理突發狀況，資源不足、同儕間汲汲追求績效，對上無從表達意見、重服從的工作情境；整體而言，則認為警察工作目標、工作範圍尚稱明確。 三、本研究從警動機調查，有33.9%的員警是「想為社會治安貢獻一己心力」為最多，而有22.9%的員警是為「喜歡警察工作」，得知我國警勤區警察之從警動機仍多有利他的理想。大致而言，從警動機主動明確，愈具理想性則其愈能明瞭工作範圍與職掌，亦認為警察之理想目標是可實現的，在行為的表現上亦較不會有推諉責任的防禦行為。 四、年紀愈輕、從警年資愈低，愈認為警察工作目標過高遠、職掌不明確，執勤所需之資源不足感愈強，而工作壓力愈大，表現推諉責任之防禦行為情形愈嚴重。 五、未婚者之推諉責任、抑制變遷、輕忽民眾等防禦行為較已婚者嚴重；有宗教信仰的同仁較不會逃避工作、推卸責任(「推諉責任」平均數較低)，對於民眾的權益及需求會積極熱心處理(「積極應事」平均數較高)。 六、勤區員警之工作考量優先順序是，50.1%的員警(925人)是個人導向（保護自己優先），38.7%的員警則為程序導向（程序合於法規優先），而有10.9%的員警是屬任務導向（達成任務優先）。個人導向者在防禦行為中的「推諉責任」、「重質輕量」、「抑制變遷」、「輕忽民眾」等4項，平均數最高和其他五組中之一至二組組間差異達顯著水準，由此可知，個人導向工作考量之警勤區警員，較易有防禦行為。 七、路徑分析結果，驗證「工作壓力」、「工作自主」及「管理自主」居於中介變項之位置，「裁量權」（含「裁量權限」及「裁量功能」）非居於中介變項位置，研究架構需作修正。 八、依多變量的區別分析法分析，彙整成2線性區別函數，函數一，可將62.64%母群體加以分類，而其餘37.36%，則可由函數二加以分類，整體正確區別率為56.56%，超過50%，而56.56%之整體區別率達顯著水準。 九、迴歸、路徑分析及區別分析皆顯示「工作壓力」、「工作目標模糊衝突」、「管理自主」、「工作自主」、「政策目標接受度」5因素為預測防禦行為之重要變數，雖先後順序有所不同。 從本研究結果顯示，目前基層普遍存在消極、無力的任事態度，此種情形與違法犯紀的重大違規事件比起來，或許微不足道，但若大部份的政策執行者都採此態度應事，那麼即使有再立意甚佳、見解精闢、規劃完善的政策計畫亦屬空中樓閣，而無法落實執行，故於實務上對於警勤區警員的工作提出以下建議： 一、業務簡化降低壓力 二、尊重基層參與決策 三、定位預防犯罪專業 四、有效溝通價值傳承 五、回應民意民眾回饋 有關後續研究則提出：精進發展預測模式，對工作2年之警勤區員警施測後分群，針對問題給予正確引導；對於員警裁量之判斷與選擇過程等做行政學上之研究探討，與「裁量權限」、「裁量功能」二因素對防禦行為之影響地位進行瞭解；警勤區警員在面臨「服務更多民眾」與「維持高品質服務」時的實際選擇；及持續定期關注瞭解我國警勤區警員防禦行為的現況，等建議。 / According to the Article 2 of the Police Act: The police are obligated to maintain public order, protect social security, prevent all hazards, and promote public welfare according to applicable laws. The work of police is all-encompassing, and the police officers are the frontline workers or policy implementers in government agencies. They are more frequently and directly interacting with citizens, they play the role of bridge between the government and the public. Because the police officers are the law enforcement and regulatory role, they affect the rights and interests of the public very seriously, so there are usually a lot of controversy, especially the police beats that are the basic unit of police duties, a key contention of the police officers in the police beats is that the decisions and actions of them, actually ‘become’, or represent, the policies of the government agencies they work for. They are very important so chosen to be the objects of this study. "Theory of Street-Level Bureaucracy" of Lipsky (1980), which is grounded in observations of the collective behavior of public service organizations and advances a theory of the work of street level bureaucracies as individual workers experience it. The behavior of street-level bureaucrats is shaped by the nature of their work and conditions in which they operate. In response to the challenges they face, street-level bureaucrats often develop routines and simplifications in an attempt to reduce complexity, gain greater control over their work and manage stress. This research was based on Lipsky's theory of street-level bureaucracy, and the “A Typology of Implementation Behaviors of Street Level Bureaucrats.” of Sorg (1983), and the “Defensive Behavior in Organizations: A Preliminary Model." of Ashforth and Lee (1990). The purpose of this study is to understand what’s the working environment and dilemmas of the police officers in the police beats? How they adapted the dilemmas? What’s the situation of the defensive behaviors of the police officers in the police beats? Why did they have these behaviors? And what are the important determinants of the defensive behaviors? This study attempts to combine the quantitative and qualitative research methods. There is a questionnaire for the police officers in the police beats, also an observant questionnaire for the sophomores of the Central Police University, while the sophomores worked as police cadets they also were observers. The questionnaire survey data was analyzed by Frequency, Reliability and Validity Analysis, Factor Analysis, Descriptive Statistics, X2, Correlation Coefficient, T Test, Variance Analysis (ANOVA), Regression Analysis, Stepwise regression, Path Analysis, Cluster Analysis, Discriminant Analysis and so on. This study’s finding are as follows: 1. There are some kinds of defensive behaviors of the police officers in the police beats such as "shirk responsibility", "neglect the people", "resist change". According to the cluster analysis, there are 618 samples (33.5%) in the "negative coping" group, 607(33%) in the "highly defensive" group and 448 in the "Positive Attendance" group, showing that 66.3% of police officers have defensive behaviors. 2. The internal and external environment of the police officers in the police beats is complex and chaotic. There are a series of dilemmas of the police officers in the police beats. 3. There are 56.8% of the police officers in the police beats serve as public employment with a commitment to serving the community. The police officers in the police beats working with more idealization are more less "shirk responsibility" behavior. 4. The younger police officers who were working less than 2 years from the police service, they think that the goal of police is too ambitious, lacking of resources, felling more working pressure, and have more serious "shirk responsibility" behavior. 5. The unmarried police officers in the police beats have more "shirk responsibility", "neglect the people" and "resist change" behaviors than the married. The police officers with religion have less "shirk responsibility" behavior. 6. The priority of the police officers in the police beats were follow: there are 50.1% of the police officers (925) are personal oriented (to protect themselves), 38.7% of the police officers are procedural oriented (the legal procedure) and 10.9% of the staff are task-oriented (to achieve the task). The personal oriented police officers have more serious defensive behaviors. 7. According to the path analysis, that the "working pressure", "work autonomy" and "manage autonomy" are the intermediary variables of the defensive behaviors. The "Discretion" is not, so the structure of research needs to be revised. 8. According to the discriminant analysis, there are 2 function, the 62.64% of the population could classify correctly by function 1, and the remaining 37.36% of the population could classify correctly by function 2. The distinction rate was 56.56 %, more than 50%, and reached a significant level. 9. According to the regression, path and discriminant analyses, that the "working pressure", "the working objectives are fuzzy and conflict", "manage autonomy", "working autonomy" and "acceptance of policy goal" 5 factors are important variables of defensive behaviors. Based on the findings above-mentioned, here are the recommendations of this study: 1. Simplify the working contents of the police officers in the police beats, and to reduce the working pressure. 2. Establish the mechanisms that the police officers in the police beats participate in decision-making. 3. Clarify the police officers in the police beats be the professional crime prevention roles. 4. Enhance internal communicant channels to preserve the heritage. 5. Respond to public opinion and build up the feedback of citizens to be the encouragement of the police officers in the police beats.

The impacts of exogenous cannabinoids, such as the chemical constituents of Cannabis sativa like cannabidiol (CBD), on brain regions having a modest number of cannabinoid receptors, for example, the ventromedial hypothalamus, are not yet surely knew. A few researches have shown evidence that ventromedial hypothalamus (VMH) neurons play a role in modulating innate fear-induced behavioural reactions in rodents submitted to experimental models of panic attack, for example those based on prey versus wild snake confrontation paradigm. The panic attack-like state was also potentially induced in laboratory animals by N-Methyl-D-aspartate (NMDA), an excitatory amino acid, which stimulates neurons that organize defensive behavioural reactions in the central nervous system. Despite the fact that CB1 receptor-mediated endocannabinoid signaling mechanism underlies the antiaversive effect of exogenous anandamide in medial hypothalamus, there is still a lack of morphological evidence to support the distribution of CB1 receptors in the VMH. Henceforth, this study was designed to explore the specific pattern of distribution of the CB1 receptors in the VMH and, subsequently, the implication of these receptors in the endocannabinoidmodulated defensive behavioural responses followed by fear-induced antinociception evoked by NMDA microinjected in the VMH. A stainless steel guide-cannula was embedded in the rodent\'s brain coordinated towards VMH by means of stareotaxic surgery. Three different doses of cannabidiol (CBD) were microinjected in the VMH. The most effective dose was used after the pretreatment with the CB1 receptor-antagonist AM251, followed by NMDA microinjection in the VMH. The outcomes demonstrated that the defensive behavioural responses evoked in response to intra-VMH administration of NMDA (6 nmol) were decreased by intra-hypothalamic microinjections of CBD at the highest dose (100 nmol).These effects, however, were blocked by the administration of the CB1 receptor-antagonist AM251 (100 pmol) in the VMH. In addition, the fear-induced antinociception elicited by VMH chemical stimulation diminished after the VMH treatment with CBD, an effect reversed by the intra-diencephalic pretreatment with AM251. These findings suggested that CBD causes panicolytic-like effects when administered in the VMH, and that antiaversive effect recruits the CB1 receptor-endocannabinoid signaling mechanism in VMH. / O papel dos canabinoides exógenos nas regiões do cérebro com um número modesto de receptores cannabinoides, por exemplo, o hipotálamo ventromedial, ainda não está plenamente esclarecido. Algumas pesquisas de nosso grupo, não obstante, mostraram o hipotálamo ventromedial (HVM) exerce modulação de reações comportamentais provocadas pelo medo inato em animais submetidos a um modelo de ataques de pânico. Crises de pânico foram induzidas em animais de laboratório por N-metil-D-aspartato (NMDA), um aminoácido excitatório que, ao ser microinjetado em estruturas do sistema encefálico de aversão, estimula reações comportamentais defensivas no sistema nervoso central que mimetizam as respostas defensivas eliciadas por roedores confrontados com serpentes. Apesar do mecanismo de sinalização endocanabinoide mediado pelos receptores CB1 desempenhar um papel na modulação da neurotransmissão excitadora e inibitória no SNC, ainda há escassez de evidências morfológicas que embasem a distribuição dos receptores CB1 no HVM. Por conseguinte, este estudo foi idealizado para explorar a forma específica de distribuição dos receptores CB1 no HVM e, posteriormente, estudar a implicação desses receptores na modulação de respostas comportamentais defensivas, seguidas por antinocicepção induzida pelo medo, moduladas por endocanabinoides e evocadas por microinjetação de NMDA no HVM. Uma cânula-guia feita de aço inoxidável foi implantada no cérebro do roedor, e direcionada para o HVM por meio de cirurgia estareotóxica. Três diferentes doses de cannabidiol (CBD) foram microinjetadas no HVM. A dosagem mais eficaz foi utilizada após o pré-tratamento do hipotálamo medial com um antagonista do receptor CB1, o AM251, seguido da microinjeção NMDA no HVM. Os resultados demonstraram que as respostascomportamentais defensivas evocadas em resposta à administração intra-HVM de NMDA (6 nmol) foram diminuídas por microinjeções intra-hipotalâmicas de CBD na dose mais alta (100 nmol). Estes efeitos, no entanto, foram atenuados pela administração do antagonista do receptor CB1, AM251, na dose de 100 pmol no HVM. Além disso, a antinocicepção induzida pelo medo foi atenuada pela administração intra-diencefálica de CBA, o que foi revertido pelo pré-tratamenot do HVM com AM251. Esses dados sugerem que o CBD causa efeitos panicolíticos, quando administrado no HVM, envolvendo o mecanismo de sinalização do receptor CB1-endocannabinoide.

A resposta comportamental de Imobilidade Tônica (IT) ocorre em situações de perigo intenso, e em situações inescapáveis, como por exemplo,o ataque de um predador. Esta resposta caracteriza-se por perda do reflexo de endireitamento e relativa falta de responsividade aos estímulos ambientais. Estudos consistentes tem demonstrado o envolvimento de distintas áreas encefálicas na modulação desta resposta, entre elas a substância cinzenta periaquedutal, o hipotálamo e a amígdala. Considerando a amígdala em particular, estudos mostraram o envolvimento dos receptores para o fator liberador de corticotropina (CRF) dos núcleos basolateral (BLA) e central (CeA) na modulação da resposta de IT em cobaias. De fato, nas últimas décadas, várias evidências sugerem que o CRF está intimamente correlacionado com comportamento emocional associado ao medo e à ansiedade. Embora seja claro o envolvimento de receptores CRF na modulação do medo, e especificamente na modulação da IT em cobaias, ainda não está esclarecido o envolvimento dos diferentes subtipos de receptores para CRF na modulação emocional. Desta forma, o objetivo deste trabalho foi investigar o envolvimento dos receptores específicos para o fator liberador de corticotropina, CRF1 e CRF2 dos núcleos basolateral (BLA) e central da amígdala (CeA) na modulação da resposta de IT em cobaias.Para atingir estes objetivos, grupos independentes de cobaias, com implante de cânulas-guias dirigidas para o BLA ou para o CeA foram avaliadas no teste de imobilidade tônica, antes e depois da administração dos antagonistas específicos para receptores CRF1 (CP-376395) ou para receptores CRF2 (Astressin 2B), ou depois da administração de CRF precedido ou não dos antagonistas CRF1 ou CRF2. Em adição, para avaliar se as drogas utilizadas alteraram a atividade locomotora, foi realizado o teste do campo aberto, por 5 minutos, após a administração dos antagonistas para receptores CRF1 (CP-376395) e CRF2 (Astressin 2B), em doses capazes de alterar a resposta de IT em cobaias, e de CRF precedido por antagonista CRF1 ou CRF2. Os resultados deste trabalho mostram que o bloqueio dos receptores CRF1 e CRF2 no BLA e no CeA reduziram a duração da resposta defensiva de imobilidade tônica (IT) em cobaias. Inversamente, a ativação destes receptores no BLA e no CeA aumentou o tempo de IT, demonstrado pela administração de CRF nestas regiões amigdalóides. Ainda, os antagonistas específicos para receptores CRF1 e CRF2 foram capazes de bloquear o aumento da duração da IT induzida pelo CRF administrado no mesmo sítio. Estes resultados sugerem que o efeito promovido pelo CRF no BLA e no CeA ocorre por atuação conjunta em receptores CRF1 e CRF2. Em adição, é importante ressaltar que as drogas, nas doses utilizadas neste estudo, não promoveram alteração da resposta motora, desde que não alteraram a atividade no teste do campo aberto, o que por si só, poderia alterar a resposta de IT. Assim, é possível que sugerir que o bloqueio específico de receptores CRF1 e CRF2 do BLA e do CeA promovem redução do medo e/ou da ansiedade, resultando em redução da resposta de IT em cobaias. / The tonic immobility response (TI ) occurs in inescapable situations of intense danger, such as the predator attack. This response is characterized by loss of righting reflex and the relative lack of responsiveness to environmental stimuli. Consistent studies have demonstrated the involvement of different brain areas to modulate this defensive behavior, including the periaqueductal gray matter, hypothalamus and amygdala. Whereas the amygdala in particular, studies have shown the involvement of receptors for corticotropin-releasing factor (CRF) of the central (CeA) and basolateral (BLA) nuclei os amygdala in TI modulating in guinea pigs. Indeed, in recent decades, several evidences suggest that CRF is closely correlated with emotional behavior associated with fear and anxiety. While it is clear the involvement of CRF receptors in the modulation of fear, and specifically in the modulation of TI, it is still unclear the involvement of different subtypes of CRF receptors in the emotional modulation. Thus, the aim of this study was to investigate the involvement of specific receptors for corticotropin-releasing factor, CRF1 and CRF2of BLA and of CeA in modulating the TI response in guinea pigs. To achieve these objectives, independent groups of guinea pigs were implanted with guide cannulae aimed for BLA or CeA were evaluated in the test of tonic immobility before and after the administration of specific antagonists of CRF1 receptors (CP- 376395) or CRF2 receptors (Astressin 2B), or after the administration of CRF preceded by CRF1or CRF2 antagonists, or CRF per se. In addition, to assess whether the drugs used altered locomotor activity, the open field test, for 5 minutes was performed after administration of antagonists for CRF1 receptors (CP- 376395) and CRF2 (Astressin 2B), at doses that alter the TI response in guinea pigs, and the CRF agonist preceded by CRF1 or CRF2. These results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA reduced the duration of the defensive response of tonic immobility (TI) in guinea pigs. In contrast, activation of these receptors in the BLA and CeA increased the TI duration, demonstrated by administration of CRF in these amygdaloid regions. Also, specific antagonists for CRF1 and CRF2 receptors were able to block the increase in the TI response induced by CRF administered in the same structure. These results suggest that the effect promoted by CRF in the BLA and CeA is by joint performance of CRF1 and CRF2 receptors. Additionally, it is important to note that the drugs, in the doses used in this study, did not promote change in the motor response, since it did not alter the activity in the open field test, which by itself could alter the TI response. Thus, it is possible to suggest that the specific blockade of CRF1 and CRF2 receptors in the BLA and CeA promote reduction of fear and/or anxiety, resulting in reduced TI response in guinea pigs.

A resposta comportamental de Imobilidade Tônica (IT) ocorre em situações de perigo intenso, e em situações inescapáveis, como por exemplo,o ataque de um predador. Esta resposta caracteriza-se por perda do reflexo de endireitamento e relativa falta de responsividade aos estímulos ambientais. Estudos consistentes tem demonstrado o envolvimento de distintas áreas encefálicas na modulação desta resposta, entre elas a substância cinzenta periaquedutal, o hipotálamo e a amígdala. Considerando a amígdala em particular, estudos mostraram o envolvimento dos receptores para o fator liberador de corticotropina (CRF) dos núcleos basolateral (BLA) e central (CeA) na modulação da resposta de IT em cobaias. De fato, nas últimas décadas, várias evidências sugerem que o CRF está intimamente correlacionado com comportamento emocional associado ao medo e à ansiedade. Embora seja claro o envolvimento de receptores CRF na modulação do medo, e especificamente na modulação da IT em cobaias, ainda não está esclarecido o envolvimento dos diferentes subtipos de receptores para CRF na modulação emocional. Desta forma, o objetivo deste trabalho foi investigar o envolvimento dos receptores específicos para o fator liberador de corticotropina, CRF1 e CRF2 dos núcleos basolateral (BLA) e central da amígdala (CeA) na modulação da resposta de IT em cobaias.Para atingir estes objetivos, grupos independentes de cobaias, com implante de cânulas-guias dirigidas para o BLA ou para o CeA foram avaliadas no teste de imobilidade tônica, antes e depois da administração dos antagonistas específicos para receptores CRF1 (CP-376395) ou para receptores CRF2 (Astressin 2B), ou depois da administração de CRF precedido ou não dos antagonistas CRF1 ou CRF2. Em adição, para avaliar se as drogas utilizadas alteraram a atividade locomotora, foi realizado o teste do campo aberto, por 5 minutos, após a administração dos antagonistas para receptores CRF1 (CP-376395) e CRF2 (Astressin 2B), em doses capazes de alterar a resposta de IT em cobaias, e de CRF precedido por antagonista CRF1 ou CRF2. Os resultados deste trabalho mostram que o bloqueio dos receptores CRF1 e CRF2 no BLA e no CeA reduziram a duração da resposta defensiva de imobilidade tônica (IT) em cobaias. Inversamente, a ativação destes receptores no BLA e no CeA aumentou o tempo de IT, demonstrado pela administração de CRF nestas regiões amigdalóides. Ainda, os antagonistas específicos para receptores CRF1 e CRF2 foram capazes de bloquear o aumento da duração da IT induzida pelo CRF administrado no mesmo sítio. Estes resultados sugerem que o efeito promovido pelo CRF no BLA e no CeA ocorre por atuação conjunta em receptores CRF1 e CRF2. Em adição, é importante ressaltar que as drogas, nas doses utilizadas neste estudo, não promoveram alteração da resposta motora, desde que não alteraram a atividade no teste do campo aberto, o que por si só, poderia alterar a resposta de IT. Assim, é possível que sugerir que o bloqueio específico de receptores CRF1 e CRF2 do BLA e do CeA promovem redução do medo e/ou da ansiedade, resultando em redução da resposta de IT em cobaias. / The tonic immobility response (TI ) occurs in inescapable situations of intense danger, such as the predator attack. This response is characterized by loss of righting reflex and the relative lack of responsiveness to environmental stimuli. Consistent studies have demonstrated the involvement of different brain areas to modulate this defensive behavior, including the periaqueductal gray matter, hypothalamus and amygdala. Whereas the amygdala in particular, studies have shown the involvement of receptors for corticotropin-releasing factor (CRF) of the central (CeA) and basolateral (BLA) nuclei os amygdala in TI modulating in guinea pigs. Indeed, in recent decades, several evidences suggest that CRF is closely correlated with emotional behavior associated with fear and anxiety. While it is clear the involvement of CRF receptors in the modulation of fear, and specifically in the modulation of TI, it is still unclear the involvement of different subtypes of CRF receptors in the emotional modulation. Thus, the aim of this study was to investigate the involvement of specific receptors for corticotropin-releasing factor, CRF1 and CRF2of BLA and of CeA in modulating the TI response in guinea pigs. To achieve these objectives, independent groups of guinea pigs were implanted with guide cannulae aimed for BLA or CeA were evaluated in the test of tonic immobility before and after the administration of specific antagonists of CRF1 receptors (CP- 376395) or CRF2 receptors (Astressin 2B), or after the administration of CRF preceded by CRF1or CRF2 antagonists, or CRF per se. In addition, to assess whether the drugs used altered locomotor activity, the open field test, for 5 minutes was performed after administration of antagonists for CRF1 receptors (CP- 376395) and CRF2 (Astressin 2B), at doses that alter the TI response in guinea pigs, and the CRF agonist preceded by CRF1 or CRF2. These results show that blockade of CRF1 and CRF2 receptors in the BLA and CeA reduced the duration of the defensive response of tonic immobility (TI) in guinea pigs. In contrast, activation of these receptors in the BLA and CeA increased the TI duration, demonstrated by administration of CRF in these amygdaloid regions. Also, specific antagonists for CRF1 and CRF2 receptors were able to block the increase in the TI response induced by CRF administered in the same structure. These results suggest that the effect promoted by CRF in the BLA and CeA is by joint performance of CRF1 and CRF2 receptors. Additionally, it is important to note that the drugs, in the doses used in this study, did not promote change in the motor response, since it did not alter the activity in the open field test, which by itself could alter the TI response. Thus, it is possible to suggest that the specific blockade of CRF1 and CRF2 receptors in the BLA and CeA promote reduction of fear and/or anxiety, resulting in reduced TI response in guinea pigs.