The Rodent-versus-wild Snake Paradigm as a Model for Studying Anxiety- and Panic-like Behaviors: Face, Construct and Predictive Validities.

Using an innovative approach to study the neural bases of psychiatric disorders, this study investigated the behavioral, morphological and pharmacological bases of panic attack-induced responses in a prey-versus-coral snake paradigm. Mesocricetus auratus was chronically treated with intraperitoneal administration of the selective serotonin uptake inhibitor paroxetine or the gamma aminobutyric acid (GABA)/benzodiazepine receptor agonist alprazolam at three different doses and were then confronted with a venomous coral snake (Micrurus frontalis, Reptilia, Elapidae). The threatened rodents exhibited defensive attention, flat back approaches, defensive immobility, and escape defensive responses in the presence of the venomous snake, followed by increases in Fos protein in limbic structure neurons. Chronic administration of both paroxetine and alprazolam decreased these responses with morphological correlates between the panicolytic effect of both drugs administered at the highest dose and decreases in Fos protein-immunolabeled perikarya found in the amygdaloid complex, hypothalamus and periaqueductal gray matter columns, which are structures that make up the encephalic aversion system. These findings provide face, construct and predictive validities of this new experimental model of anxiety- and panic attack-like behavioral responses displayed by threatened prey confronted with venomous coral snakes.

µ-Opioid and 5-HT1A receptors in the dorsomedial hypothalamus interact for the regulation of panic-related defensive responses.

The dorsomedial hypothalamus (DMH) and the dorsal periaqueductal gray (DPAG) have been implicated in the genesis and regulation of panic-related defensive behaviors, such as escape. Previous results point to an interaction between serotonergic and opioidergic systems within the DPAG to inhibit escape, involving µ-opioid and 5-HT1A receptors (5-HT1AR). In the present study we explore this interaction in the DMH, using escape elicited by electrical stimulation of this area as a panic attack index. The obtained results show that intra-DMH administration of the non-selective opioid receptor antagonist naloxone (0.5 nmol) prevented the panicolytic-like effect of a local injection of serotonin (20 nmol). Pretreatment with the selective µ-opioid receptor (MOR) antagonist CTOP (1 nmol) blocked the panicolytic-like effect of the 5-HT1AR agonist 8-OHDPAT (8 nmol). Intra-DMH injection of the selective MOR agonist DAMGO (0.3 nmol) also inhibited escape behavior, and a previous injection of the 5-HT1AR antagonist WAY-100635 (0.37 nmol) counteracted this panicolytic-like effect. These results offer the first evidence that serotonergic and opioidergic systems work together within the DMH to inhibit panic-like behavior through an interaction between µ-opioid and 5-HT1A receptors, as previously described in the DPAG.

Panicolytic-like action of bradykinin in the dorsal periaqueductal gray through µ-opioid and B2-kinin receptors.

A wealth of evidence has shown that opioid and kinin systems may control proximal defense in the dorsal periaqueductal gray matter (dPAG), a critical panic-associated area. Studies with drugs that interfere with serotonin-mediated neurotransmission suggest that the µ-opioid receptor (MOR) synergistically interacts with the 5-HT1A receptor in the dPAG to inhibit escape, a panic-related behavior. A similar inhibitory effect has also been reported after local administration of bradykinin (BK), which is blocked by the non-selective opioid receptor antagonist naloxone. The latter evidence, points to an interaction between BK and opioids in the dPAG. We further explored the existence of this interaction through the dPAG electrical stimulation model of panic. We also investigated whether intra-dPAG injection of captopril, an inhibitor of the angiotensin-converting enzyme (ACE) that also degrades BK, causes a panicolytic-like effect. Our results showed that intra-dPAG injection of BK inhibited escape performance in a dose-dependent way, and this panicolytic-like effect was blocked by the BK type 2 receptor (B2R) antagonist HOE-140, and by the selective MOR antagonist CTOP. Conversely, the panicolytic-like effect caused by local administration of the selective MOR agonist DAMGO was antagonized by pre-treatment with either CTOP or HOE-140, indicating cross-antagonism between MOR and B2R. Finally, intra-dPAG injection of captopril also impaired escape in a dose-dependent way, and this panicolytic-like effect was blocked by pretreatment with HOE-140, suggesting mediation by endogenous BK. The panicolytic-like effect of captopril indicates that the use of ACE inhibitors in the clinical management of panic disorder may be worth exploring.

Participation of dorsal periaqueductal gray 5-HT1A receptors in the panicolytic-like effect of the κ-opioid receptor antagonist Nor-BNI.

Panic patients may have abnormalities in serotonergic and opioidergic neurotransmission. The dorsal periaqueductal gray (dPAG) plays an important role in organizing proximal defense, related to panic attacks. The 5-HT1A receptor (5-HT1A-R) is involved in regulating escape behavior that is organized in the dPAG. Activation of κ-opioid receptor (KOR) in this region causes anxiogenic effects. In this study, we investigated the involvement of KOR in regulating escape behavior, using systemic and intra-dPAG injection of the KOR antagonist Nor-BNI. As panic models, we used the elevated T-maze (ETM) and the dPAG electrical stimulation test (EST). We also evaluated whether activation of the 5-HT1A-R or the µ-opioid receptor (MOR) in the dPAG contributes to the Nor-BNI effects. The results showed that systemic administration of Nor-BNI, either subcutaneously (2.0 and 4.0mg/kg) or intraperitoneally (2.0mg/kg), impaired escape in the EST, indicating a panicolytic-like effect. Intra-dPAG injection of this antagonist (6.8nmol) caused the same effect in the EST and in the ETM. Association of ineffective doses of Nor-BNI and the 5-HT1A-R agonist 8-OH-DPAT caused panicolytic-like effect in these two tests. Previous administration of the 5-HT1A-R antagonist WAY-100635, but not of the MOR antagonist CTOP, blocked the panicolytic-like effect of Nor-BNI. These results indicate that KOR enhances proximal defense in the dPAG through 5-HT1A-R modulation, independently of MOR. Because former results indicate that the 5-HT1A-R is involved in the antipanic action of antidepressants, KOR antagonists may be useful as adjunctive or alternative drug treatment of panic disorder.

Disinhibition of the rat prelimbic cortex promotes serotonergic activation of the dorsal raphe nucleus and panicolytic-like behavioral effects.

Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic. We used the elevated T-maze model and Vogel conflict test to evaluate defensive responses associated with anxiety or panic. The results showed that intra-PL PIC caused an increase in c-Fos activation in serotonergic cells in DR subregions. Furthermore, the intra-PL injection of PIC induced a panicolytic-like effect without affecting behaviors associated with anxiety. Our findings suggest that the PL-DR pathway, through DR serotonergic stimulation, is involved in the control of panic-related behaviors by control of serotonin release in structures that modulate panic responses, such as the dorsal periaqueductal gray.

Deep brain stimulation of the dorsal raphe inhibits avoidance and escape reactions and activates forebrain regions related to the modulation of anxiety/panic.

One of the main neurochemical systems associated with anxiety/panic is the serotonergic system originating from the dorsal raphe nucleus (DR). Previous evidence suggests that the DR is composed of distinct subpopulations of neurons, both morphologically and functionally distinct. It seems that mainly the dorsal region of the DR (DRD) regulates anxiety-related reactions, while lateral wings DR (lwDR) serotonin (5-HT) neurons inhibit panic-related responses. In this study we used the technique of deep brain stimulation (DBS) to investigate the role played by the DRD and lwDR in defense. Male Wistar rats were submitted to high-frequency stimulation (100µA, 100Hz) in one of the two DR regions for 1h and immediately after tested in the avoidance or escape tasks of the elevated T-maze (ETM). In clinical terms, these responses have been related to generalized anxiety and panic disorder, respectively. After being submitted to the ETM, animals were placed in an open field for locomotor activity assessment. An additional group of rats was submitted to DBS of the DRD or the lwDR and used for quantification of c-Fos immunoreactive (Fos-ir) neurons in brain regions related to the modulation of defense. Results showed that stimulation of the DRD decreased avoidance latencies, an anxiolytic-like effect. DRD stimulation also led to increases in Fos-ir in the medial amygdala, lateral septum and cingulate cortex. DBS applied to the lwDR increased escape latencies, a panicolytic-like effect. This data highlights the importance of raphe topography and the potential benefit of the DBS technique for the treatment of anxiety-related disorders.

Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour.

The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic-like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non-oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic-like behaviour. The chemical stimulation of the VMH with 9nmol of N-methyl-d-aspartic acid (NMDA) elicited oriented and non-oriented escape behaviours. The pretreatment of the dPAG with a non-selective blocker of synaptic contacts, cobalt chloride (CoCl2), followed by stimulation of the dorsomedial part of the ventromedial hypothalamus (dmVMH) with 9nmol of NMDA, abolished the non-oriented/explosive escape and freezing responses elicited by the stimulation of the dmVMH. Nonetheless, the rats still showed oriented escape to the burrow. On the other hand, when the blockade of the dmVMH with CoCl2 was followed by stimulation of the dPAG with 6nmol of NMDA, no effect was observed either on the non-oriented/explosive escape or on the freezing behaviour organised by the dPAG. Furthermore, Fos protein-labelled neurons were observed in the dPAG after the stimulation of the dmVMH with 9nmol of NMDA. Additionally, when the anterograde neurotracer biotinylated dextran amine (BDA) was deposited in the dmVMH subsequent stimulation of the dmVMH produced BDA-labelled neural fibres with terminal boutons surrounding Fos-labelled neurons in the dPAG, suggesting synaptic contacts between dmVMH and dPAG neurons for eliciting panic-like behavioural responses. The current data suggest that the dPAG is the key structure that organises non-oriented/explosive escape reactions associated with panic attack-like behaviours.

Experimental study on the effects of anxiety sensitivity and somatosensory amplification on the response to the 35% CO2 challenge in abstinent smokers.

The relationship between nicotine abstinence and panic onset is still not well understood and the role of catastrophic misinterpretation, as possible moderator or mediator of this relationship, is unknown. We tested whether nicotine abstinence influences the response to a CO2 panic challenge and whether catastrophic misinterpretation (measured via the Anxiety Sensitivity [ASI] and the SomatoSensory Amplification Scale [SSAS]) exerts a moderating or mediating effect on the relationship between nicotine abstinence and panic. Eighty regular smokers underwent a 35% CO2 challenge after the transdermal administration of nicotine or placebo. Physiological and psychological variables were measured at baseline, directly before and after the challenge. Fear reactivity to the challenge was similar in both conditions. ASI (post-Test Visual Analogous Scale of Fear: ΔR² = 0.043, p < .05) and SSAS (post-Test Visual Analogous Scale of Anxiety: ΔR² = 0.036, p < .05; post-Test Panic Symptom List: ΔR² = 0.035, p < .05) influenced anxiety as response to the challenge. We found no support for the moderational and the mediational hypotheses. The findings regarding fear reactivity when group status is considered partly confirm the literature. The positive findings observed for ASI and SSAS as factors influencing the response to the challenge, together with the lack of evidence for a moderational and a mediational hypothesis, confirm that anxiety sensitivity and somatosensory amplification are independent constructs and suggest that they directly influence the response to the challenge.

The role of distress intolerance for panic and nicotine withdrawal symptoms during a biological challenge.

BACKGROUND: Distress intolerance is linked to the maintenance of panic disorder and cigarette smoking, and may underlie both problems. METHOD: Smokers (n = 54; 40.7% panic disorder) were recruited for an experimental study; half were randomly assigned to 12-hour nicotine deprivation and half smoked as usual. The current investigation consisted of secondary, exploratory analyses from this larger experimental study. Four distress intolerance indices were examined as predictors of anxious responding to an emotional elicitation task (10% carbon dioxide (CO2)-enriched air challenge); anxious responding was in turn examined as a predictor of post-challenge panic and nicotine withdrawal symptoms. RESULTS: The Distress Tolerance Scale (DTS) was significantly negatively associated with anxious responding to the challenge (ß = -0.41, p = 0.017). The DTS was negatively associated with post-challenge increases nicotine withdrawal symptoms indirectly through the effect of anxious responding to the challenge (b = -0.485, CI95% (-1.095, -0.033)). This same indirect effect was found for post-challenge severity of panic symptoms (b = -0.515, CI95% (-0.888, -0.208)). The DTS was directly predictive of post-challenge increases nicotine withdrawal symptoms, in the opposite direction (ß = 0.37, p = 0.009), but not panic symptom severity. CONCLUSIONS: Anxious responding in response to stressful experiences may explain the impact of perceived distress intolerance on panic and nicotine withdrawal symptom expression.

Interaction between µ-opioid and 5-HT1A receptors in the regulation of panic-related defensive responses in the rat dorsal periaqueductal grey.

A wealth of evidence indicates that the activation of 5-HT1A and 5-HT2A receptors in the dorsal periaqueductal grey matter (dPAG) inhibits escape, a panic-related defensive behaviour. Results that were previously obtained with the elevated T-maze test of anxiety/panic suggest that 5-HT1A and µ-opioid receptors in this midbrain area work together to regulate this response. To investigate the generality of this finding, we assessed whether the same cooperative mechanism is engaged when escape is evoked by a different aversive stimulus electrical stimulation of the dPAG. Administration of the µ-receptor blocker CTOP into the dPAG did not change the escape threshold, but microinjection of the µ-receptor agonist DAMGO (0.3 and 0.5 nmol) or the 5-HT1A receptor agonist 8-OHDPAT (1.6 nmol) increased this index, indicating a panicolytic-like effect. Pretreatment with CTOP antagonised the anti-escape effect of 8-OHDPAT. Additionally, combined administration of subeffective doses of DAMGO and 8-OHDPAT increased the escape threshold, indicating drug synergism. Therefore, regardless of the aversive nature of the stimulus, µ-opioid and 5-HT1A receptors cooperatively act to regulate escape behaviour. A better comprehension of this mechanism might allow for new therapeutic strategies for panic disorder.

Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel?

First reported formally in 1980, the frequent ability of infectious fever to relieve autistic behavior, often dramatically (and rarely aggravate), has long tantalized parents, practitioners, and researchers - yet its physiology and biochemistry have never been investigated, to judge from the literature. Fever is a complex interplay of immune, metabolic, and stress responses, yet its benefit in autistic disorders (ASD) may derive largely from a single response - release of the amino acid glutamine from skeletal muscles as provisional fuel. This proposal is based on evidence of low blood and brain glutamine in ASD children and adults, notable lack of autistic behavior in children with high brain glutamine from urea cycle disorders, and other events that elicit dramatic improvements - fasting, panic, pain, and the corticosteroid prednisone - that release or synthesize glutamine. Glutamine released from muscles is metabolized by the intestines like ingested glutamine. If glutamine released by fever rarely aggravates autistic behavior, why would supplemental glutamine?

Orexin 1 receptors are a novel target to modulate panic responses and the panic brain network.

BACKGROUND: Although the hypothalamic orexin system is known to regulate appetitive behaviors and promote wakefulness and arousal (Sakurai, 2007 [56]), this system may also be important in adaptive and pathological anxiety/stress responses (Suzuki et al., 2005 [4]). In a recent study, we demonstrated that CSF orexin levels were significantly higher in patients experiencing panic attacks compared to non-panicking depressed subjects (Johnson et al., 2010 [9]). Furthermore, genetically silencing orexin synthesis or blocking orexin 1 receptors attenuated lactate-induced panic in an animal model of panic disorder. Therefore, in the present study, we tested if orexin (ORX) modulates panic responses and brain pathways activated by two different panicogenic drugs. METHODS: We conducted a series of pharmacological, behavioral, physiological and immunohistochemical experiments to study the modulation by the orexinergic inputs of anxiety behaviors, autonomic responses, and activation of brain pathways elicited by systemic injections of anxiogenic/panicogenic drugs in rats. RESULTS: We show that systemic injections of two different anxiogenic/panicogenic drugs (FG-7142, an inverse agonist at the benzodiazepine site of the GABA(A) receptor, and caffeine, a nonselective competitive adenosine receptor antagonist) increased c-Fos induction in a specific subset of orexin neurons located in the dorsomedial/perifornical (DMH/PeF) but not the lateral hypothalamus. Pretreating rats with an orexin 1 receptor antagonist attenuated the FG-7142-induced anxiety-like behaviors, increased heart rate, and neuronal activation in key panic pathways, including subregions of the central nucleus of the amygdala, bed nucleus of the stria terminalis, periaqueductal gray and in the rostroventrolateral medulla. CONCLUSION: Overall, the data here suggest that the ORX neurons in the DMH/PeF region are critical to eliciting coordinated panic responses and that ORX1 receptor antagonists constitute a potential novel treatment strategy for panic and related anxiety disorders. The neural pathways through which ORX1 receptor antagonists attenuate panic responses involve the extended amygdala, periaqueductal gray, and medullary autonomic centers.

Main and interactive effects of emotion dysregulation and breath-holding duration in relation to panic-relevant fear and expectancies about anxiety-related sensations among adult daily smokers.

The current study investigated the main and interactive effects of emotion dysregulation and distress tolerance in relation to panic-relevant variables among daily smokers. The sample consisted of 172 adults (61.2% male; M(age)=31.58, SD=11.51), who reported smoking an average of 15.99 cigarettes per day (SD=10.00). Results indicated that both emotion dysregulation and distress tolerance were significantly related to interoceptive fear and agoraphobia. Additionally, emotion dysregulation, but not distress tolerance, was significantly related to anxiety sensitivity. All effects were evident above and beyond the variance accounted for by average cigarettes per day, tobacco-related physical illness, and panic attack history. The interaction between emotion dysregulation and distress tolerance significantly predicted interoceptive and agoraphobic fears as well as the cognitive component of anxiety sensitivity. Such findings underscore the importance of emotion dysregulation and distress tolerance in regard to panic-specific fear and expectancies about anxiety-related sensations among daily smokers.

"The booklet helped me not to panic": a pilot of a decision aid for asymptomatic women with ovarian cancer and with rising CA-125 levels.

INTRODUCTION: After first-line treatment, cancer antigen 125 (CA-125) levels can rise many months before there are other signs of recurrent ovarian cancer, leading to a difficult choice about when to initiate second-line treatment. To assist with shared decision making, a decision aid (DA) booklet that compared the options of "wait and see," chemotherapy, and tamoxifen was developed and piloted. METHODS: Twenty patients attending clinics at 2 cancer centers agreed to read the DA booklet, complete a set of standardized and purpose-designed measures, and provide feedback on the DA booklet via a semistructured telephone interview. Participants were either currently making the decision about treatment (n = 14) or had progressed and were now receiving treatment of recurrent cancer (n = 6). RESULTS: Most patients found information in the DA easy to understand (79%) and presented in a balanced way (90%), and almost all (95%) would recommend the booklet to others facing a similar decision. Women showed a good understanding of information contained in the booklet, with a mean of 88% answering each of the knowledge questions correctly. Compared with other ovarian cancer studies, decisional conflict scores were lower, whereas anxiety scores were high but similar to 1 comparable study. Suggestions for improvement related to information about recurrent ovarian cancer and the decision making worksheets. CONCLUSIONS: The DA seems an acceptable and useful decision making resource in this setting. Strategies for reducing anxiety levels linked to booklet administration are outlined. The DA has been revised to reflect pilot findings and changes in clinical evidence, and the effectiveness of the DA in reducing decisional conflict and regret is being evaluated in a randomized controlled trial.

Increased plasma corticosterone levels after periaqueductal gray stimulation-induced escape reaction or panic attacks in rats.

The hypothalamo-pituitary-adrenal (HPA) axis is involved in stress, depression and anxiety. Controversy exists on HPA axis activation during panic attacks (PAs). We examined whether the HPA axis is involved in the escape or panic-like response in an animal model of PAs induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats. Additionally, rats were also treated with chronic administration of buspirone (BUSP) and escitalopram (ESCIT), respectively; and they were stimulated in the open-field arena for panic-like reaction. Levels of stress hormone corticosterone were measured following 30 min after escape or panic condition. Our results demonstrated that the levels of plasma corticosterone were significantly increased after the induction of escape or panic-like response in comparison with the sham animals. The levels of corticosterone were significantly decreased in the dlPAG stimulated groups after rats were treated chronically with the ESCIT but not the BUSP as compared to the saline treated animals. Importantly, the increase of corticosterone level after escape or panic-like response was paralleled by an increase of neuronal activation of c-Fos in both the parvocellular and magnocellular paraventricular nucleus of the hypothalamus. Moreover, the c-Fos data also showed a decrease in the number of positive cells particularly for the ESCIT as well as the BUSP in comparison with the saline stimulated animals. In conclusion, the present study clearly demonstrated that PA or escape response activates the HPA axis and it remains difficult to anticipate the mechanism underlying HPA axis during PAs and its relationship with 5-HT drugs.

A selective, non-peptide CRF receptor 1 antagonist prevents sodium lactate-induced acute panic-like responses.

Corticotropin releasing factor (CRF) is implicated in a variety of stress-related disorders such as depression and anxiety, and blocking CRF receptors is a putative strategy for treating such disorders. Using a well-studied animal model of panic, we tested the efficacy of JNJ19567470/CRA5626, a selective, non-peptidergic CRF type 1 receptor (CRF1) antagonist (3, 10 and 40 mg/kg intraperitoneal injection), in preventing the sodium lactate (NaLac)-induced panic-like behavioural and cardiovascular responses. Adult male rats with chronic reduction of GABA levels (by inhibition of GABA synthesis with l-allyglycine, a glutamic acid decarboxylase inhibitor) in the dorsomedial/perifornical hypothalamus are highly anxious and exhibit physiological and behavioural responses to intravenous NaLac infusions similar to patients with panic disorder. These 'panic-prone' rats pre-treated with vehicle injections displayed NaLac-induced increases in autonomic responses (i.e. tachycardia and hypertensive responses), anxiety-like behaviour in the social interaction test, and flight-like increases in locomotor activity. However, systemically injecting such panic-prone rats with the highest dose of CRF1 receptor antagonist prior to NaLac infusions blocked all NaLac-induced behaviour and cardiovascular responses. These data suggest that selective CRF1 receptor antagonists could be a novel target for developing anti-panic drugs that are as effective as benzodiazepines in acute treatment of a panic attack without the deleterious side-effects (e.g. sedation and cognitive impairment) associated with benzodiazepines.

Reflexões sobre um caso de síndrome de pânico enfocando os acontecimentos de corpo / Reflections on a case of panic disorder with focus on the corporal demeanors

O presente estudo propõe analisar os sintomas físicos manifestados na Síndrome de Pânico, enfocando-os não como reações fisiológicas, mas como eles se organizam, psiquicamente, ou seja, como "acontecimento corporal", no sentido tomado por Lacan, ao se referir clínica do real. Isso quer dizer que o sinthoma se utilizará do semblante como tentativa de articular o imaginário ao real. Miller fala sobre um acontecimento de gozo que denuncia a chegada do singular no sinthoma. Trata-se de um segmento da pesquisa psicanalítica desenvolvida para efeito de dissertação de mestrado no Programa de Pó-graduação em Psicologia Clínica da UNICAP, na qual utilizamos fragmentos de um caso clínico de um jovem do sexo masculino, casado, cujo diagnóstico psiquiátrico foi de Síndrome de Pânico, visando investigar as significações metapsicológicas dos sintomas físicos manifestados. Neste artigo, privilegiaremos nossas discussões em torno das significações dadas pelo paciente a seus sintomas corporais, distinguindo-as das manifestações fisiológicas desencadeadas pelo pânico, descritas na síndrome. As representações corporais foram entendidas como uma memória corporal que se manifesta na transferência. Nosso propósito foi mostrar nossa compreensão de como se organiza psiquicamente o acontecimento corporal nesse caso clínico, utilizando o método de interpretações proposto pela psicanálise. Como referencial teórico para discussão dessas questões, tomamos as contribuições freudianas pela ótica de Bastos, e também de autores contemporâneos que tratam do corpo na clínica, como Paul-Laurent Assoun, Piera Aulagnier, Ivanise Fontes e Maria Helena Fernandes. A análise de tais fragmentos revela que é possível identificar, por intermédio do acontecimento de corpo manifesto nos sintomas físicos do pânico, a organização da subjetividade nascente.

This study aims at analysing the physical symptoms manifested in by panic disorder - not only its merely physiological reactions - but also the way they are psychologically organized, that is to say, "the corporal demeanour" as viewed by Lacan, when referring to the clinic of real in the sinthome will make use of the semblance in an attempt to articulate the imaginary to the real. Millers refers to a jouissance which reveals the arrival of the singular into the sinthome. It is a segment of the psychoanalytic research, - carried out as master of Arts, Dissertation in the Graduate Program on Clinical Psychology at UNICAP - on which we will use fragments of a clinical case young man, married, whose psychiatric diagnosis is Panic Disorder. Our purpose is to search metapsychological meanings and the patient in relation to his corporal symptoms, by means of distinction between such meanings and the physiological manifestations caused by panic, described on the disorder. The corporal representations will be taken as a corporal memory that is revealed on the disorder. The corporal representations will be taken as a corporal memory that is revealed on the transfer. Our aims is to comprehend, with the analysis of the fragments of the studied case, how the corporal demeanour organizes itself psychologically, by means of the interpretation method suggested by psychoanalysis. As theoretical basis for discussion of such issues, we will consider Freud's ideas, according to Basto's view as well as contemporary authors who treat the body in clinic, like Paul-Laurent Assoun, Piera Aulagnier, Ivanise Fontes and Maria Helena Fernandes. The analysis of the fragments indicates that it is possible to identify the organization of the rising subjectiveness thorough body demeanor - present in the physical symptoms of panic.

Anxiety sensitivity and panic reactivity to bodily sensations: relation to quit-day (acute) nicotine withdrawal symptom severity among daily smokers making a self-guided quit attempt.

The current investigation explored the main and interactive effects of panic attacks in response to laboratory-induced bodily sensations and anxiety sensitivity in predicting acute nicotine withdrawal symptoms among daily smokers making a self-guided quit attempt. Participants were 99 daily smokers (58% women; M(age) = 28.4 years, SD = 11.7) who completed a battery of questionnaires, a voluntary hyperventilation challenge, and a measure of nicotine withdrawal symptoms 12 hr after making a self-guided quit attempt. Results indicated that the interaction of anxiety sensitivity and panic responsivity to the challenge predicted quit-day nicotine withdrawal symptom severity above and beyond the main effects (p < .05). The form of the interaction indicated that the relationship between postchallenge panic attack status and acute nicotine withdrawal was more robust among individuals who were low in anxiety sensitivity. Individuals who did not experience a panic attack posthyperventilation who were also low in anxiety sensitivity reported the lowest levels of nicotine withdrawal. Results suggest that anxiety sensitivity may be less relevant with regard to acute nicotine withdrawal severity among individuals with panic-related problems.

High-frequency stimulation of the dorsolateral periaqueductal gray and ventromedial hypothalamus fails to inhibit panic-like behaviour.

Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) and one of its target structures, the ventromedial hypothalamus (VMH), produces a typical behaviour in rats consisting of vigorous running and jumping which is known as "escape behaviour". Escape behaviour in rodents closely mimics panic attacks in humans. Since electrical stimulation at higher frequencies generally inhibits the stimulated region, we tested in this study the hypothesis that deep brain stimulation (DBS) of the dlPAG and VMH at higher frequencies (> 100 Hz) would not induce escape behaviour. More specifically, we evaluated whether experimental DBS could be used to inhibit panic-like behaviour. Rats underwent implantation of DBS-electrodes at the level of the dlPAG and VMH and the effects of various stimulation parameters were assessed. In addition, we studied the neural activation pattern resulting from DBS of the dlPAG and VMH using c-Fos immunohistochemistry. We found that stimulation amplitude is the most important stimulation parameter in the induction of escape behaviour. Remarkably, stimulation frequency (1-300 Hz) had no effect on stimulation-induced escape behaviour and therefore it was not possible to prevent the induction of escape behaviour with higher frequencies. The neuronal activation pattern resulting from dlPAG and VMH DBS was similar. These findings suggest that DBS of the dlPAG and VMH induces panic-related behaviours even at higher frequencies.

Fear reactivity to bodily sensations among heavy smokers and nonsmokers.

Individuals who smoke are more likely to experience panic attacks and develop panic disorder than those in the general population. One possible explanation is that smokers may experience a heightened fear response to somatic disturbances. To date, few laboratory studies have tested this hypothesis directly. The present study examined 24 adult heavy smokers (10 females) in 12-hr nicotine withdrawal and 24 adult nonsmokers (12 females) on subjective and physiological reactivity to a 4-min carbon dioxide rebreathing challenge. Results indicate that, despite an attenuated acceleration in respiration during the challenge, smokers experienced a significantly greater increase in self-reported panic symptoms than nonsmokers. In addition, smokers reported significantly greater trait levels of suffocation fear prior to the challenge. Findings are discussed with respect to the role of smoking in panic vulnerability.