The present study investigated the effects of suggested analgesia and level of hypnotic susceptibility (high vs. low) on acute radiant heat pain using a signal detection theory model. A signal detection paradigm was used in order to differentiate between sensitivity (sensory-discriminative) and respose bias (motivational-affective) components of pain. Treatments consisted of: (1) a suggested analgesia group, and (2) an expectancy control group. Both groups had equal numbers of high and low scorers on a scale of hypnotic susceptibility. Subjects were 32 male and female undergraduate volunteers assigned equally to each of the two treatment groups and counterbalanced for level of hypnotic susceptibility. Five levels of radiant heat (including zero) were presented. Each subject received 30 stimulus presentations per level and rated each stimulus on a scale from zero to six, with seven being a withdrawal. Self-report inventories of trait and state anxiety were also taken. Subjects participated in pre- and posttreatment sessions of radiant heat stimulation and were given three training sessions in the interim. Results were that sensitivity measures showed a significant decrease for the suggested analgesia group for all but the highest stimulus level paired comparison. There was also a decrease in sensitivity for the expectancy control group for the lowest stimulus pair. Measures of response bias for a report of pain or higher changed nondifferentially across groups and levels, except for the highest stimulus pair, for which the experimental group showed a significant hesitancy to respond relative to the control group. There were no significant difference in terms of treatment effects for high vs. low hypnotic susceptibility. Mean pain ratings decreased for both groups. Trait anxiety did not but state anxiety did decrease significantly after treatment. Results were taken as supporting Gate Control Theory and a figure-ground realignment model of pain. Suggestions were made for directions in future research. / Doctor of Philosophy

This essay investigates what may constitute a hypnotic digital artefact from a design standpoint. This essay is meant to help designers who want to create hypnotic digital artefacts in the shape of a game, or researchers who wants to further this field. With a case study analysing the game Cultist Simulator, this essay observes applications from this essay’s frameworks: NLP, Procedural Rhetorics, Flow, Trance, and Ericksonian Hypnosis. The case study serves to demonstrate how a larger scale reflection of intrinsic cross over points between hypnosis and the video game medium may take place within state-of-the-art discourse. This essay fulfils its design-aid purpose by charting factors that can be put in place to facilitate a trance and a hypnosis in a game, in a design table summarising design methods discussed. The means that may put a player’s mind in abeyance are posited here regarding how this may influence the game experience, including induction techniques, where suggestions are provided in how these might translate to a game format. Through its frameworks and case study, hypnotic content generation is put in focus, where this essay finds that games utilising metaphors and depicting inner spaces carry significance in this pursuit. It also finds that mirroring communication of the unconscious, such as adhering to rules of a dream state, and acknowledging the unconscious’ uses and capacities, has potential in this pursuit. Importantly, the essay includes a discussion on Cultist Simulator’s decadent aesthetics and its role in leading a player towards an alternate state of consciousness.

Cognitive therapy for the treatment of depression has generated substantial research indicating its effectiveness and it is currently considered among the most viable conceptualizations of depression. However, it has remained controversial because its methods do not directly address emotional symptoms in depressed persons. Treatment of depressed emotions is a primary focus of hypnotic mood elevating techniques. These techniques enable depressed persons to experience positive emotions during hypnosis sessions and to re-experience them daily concurrent with performance of certain specified behaviors. This study evaluated the efficacy of a multicomponent treatment which combines the techniques of cognitive therapy and hypnotic mood elevation in the treatment of depressed persons. The three treatment conditions constructed for this investigation were cognitive therapy plus hypnotic mood elevation, cognitive therapy plus pseudo-biofeedback, and no treatment waiting list.

O objetivo deste trabalho foi avaliar a toxicidade e ação hipnótico/sedativa e ansiolítica de um extrato seco nebulizado de Passiflora alata (PA) (2,6 % flavonóides totais), administrado pela via oral, nos testes de potenciação do sono barbitúrico, locomoção espontânea, coordenação motora, indução de catatonia, labirinto em cruz elevado, convulsões induzidas por pentilenotetrazol e temperatura corporal. PA foi administrado agudamente nas doses de 300, 600 e 900 mg/kg e por 14 dias, 300 mg/kg. Para avaliação da toxicidade aguda, foram empregadas doses de 600 a 4800 mg/kg. A genotoxicidade foi avaliada em camundongos (150, 300 e 600 mg/kg), pelo ensaio cometa alcalino. PA 300 mg/kg reduziu a latência e potenciou o tempo de sono barbitúrico. Em nenhuma das doses testadas, PA causou redução na locomoção espontânea, efeito catatônico ou prejuízos no desempenho em aparelho de rota-rod. O extrato (300 e 600 mg/kg) apresentou efeito hipotérmico. A administração aguda de PA não foi ativa no labirinto em cruz elevado e a administração repetida (300 mg/kg) provocou efeito ansiogênico. A administração aguda (300 e 600 mg/kg) ou repetida (300 mg/kg) de PA não alterou o número e a severidade das convulsões induzidas por pentilenotetrazol. Na avaliação da toxicidade aguda, não ocorreram mortes até a dose de 4800 mg/kg. Ratos tratados repetidamente com PA não apresentaram alterações significativas em parâmetros bioquímicos, hematológicos e histopatológicos, mas apresentaram sinais de irritabilidade e não mostraram ganho de massa corporal. A administração aguda de PA provocou danos no DNA (classe 4), determinados pelo ensaio cometa, em células do cérebro, fígado e sangue periférico. Os resultados obtidos para o extrato demonstram que PA administrado agudamente apresenta efeito hipnótico desprovido de efeito ansiolítico, sedativo ou comprometimento das funções motoras. Estes resultados podem explicar o efeito relatado pela população como agente indutor de sono, mas não apóiam o uso popular como calmante. Pelo contrário, o efeito ansiogênico e a toxicidade genética observados determinam à necessidade de cautela e a realização de mais estudos para a utilização de P. alata como matériaprima para a produção de medicamentos. / The aim of this work was to evaluate the toxicity and hypnotic/secative and anxiolytic effects of an aqueous spray-dried extract of P. alata (PA) (2.6% flavonoids), administrated by oral route, on barbiturate sleeping time, spontaneous locomotion, motor coordination, catalepsy induction, elevated plus-maze, pentilenotetrazole-induced convulsions and body temperature tests. In the acute treatment the doses ranged from 300 to 900 mg/kg; 300 mg/kg was used as repeated treatment. Genotoxicity was evaluated by ex vivo alkaline comet assay in mice (150, 300 and 600 mg/kg). PA 300 mg/kg decreased the latency and increased the barbiturate sleeping time. None of the tested doses of PA reduced spontaneous locomotion, induced catalepsy or performance deficit in rota-rod apparatus. Hypothermic effect was observed after administrating PA 300 and 600 mg/kg. The acute administration was not active on elevated plus-maze while repeated treatment (300 mg/kg) showed anxiogenic effect in this test. The acute (300 and 600 mg/kg) or repeated (300 mg/kg) administration of PA did not modify the number and severity of pentilenotetrazole-induced convulsions. In acute toxicity evaluation, mice deaths were not observed up to 4800 mg/kg. Rats repeatedly treated with aqueous extract did not present biochemical, hematological or histopathological significant alterations. However, the animals showed signs of irritability and did not increase body weight. In addition, mice acutely treated with PA presented DNA damage (class 4) determined by alkaline comet assay in brain, liver and peripheral blood cells. In conclusion, PA acute administration provokes hypnotic effect, destitute of anxiolytic and sedative effects and without concerning to motor functions. These results could explain the popular use as agent sleeping inductive, but they do not support the popular use, or commercialization, as tranquilizer/anxiolytic. On the contrary, the observed anxiogenic effect and genotoxicity request prudence and more studies in order to assure the efficacy and safety of utilization of P. alata with medicinal purposes.

O objetivo deste trabalho foi avaliar a toxicidade e ação hipnótico/sedativa e ansiolítica de um extrato seco nebulizado de Passiflora alata (PA) (2,6 % flavonóides totais), administrado pela via oral, nos testes de potenciação do sono barbitúrico, locomoção espontânea, coordenação motora, indução de catatonia, labirinto em cruz elevado, convulsões induzidas por pentilenotetrazol e temperatura corporal. PA foi administrado agudamente nas doses de 300, 600 e 900 mg/kg e por 14 dias, 300 mg/kg. Para avaliação da toxicidade aguda, foram empregadas doses de 600 a 4800 mg/kg. A genotoxicidade foi avaliada em camundongos (150, 300 e 600 mg/kg), pelo ensaio cometa alcalino. PA 300 mg/kg reduziu a latência e potenciou o tempo de sono barbitúrico. Em nenhuma das doses testadas, PA causou redução na locomoção espontânea, efeito catatônico ou prejuízos no desempenho em aparelho de rota-rod. O extrato (300 e 600 mg/kg) apresentou efeito hipotérmico. A administração aguda de PA não foi ativa no labirinto em cruz elevado e a administração repetida (300 mg/kg) provocou efeito ansiogênico. A administração aguda (300 e 600 mg/kg) ou repetida (300 mg/kg) de PA não alterou o número e a severidade das convulsões induzidas por pentilenotetrazol. Na avaliação da toxicidade aguda, não ocorreram mortes até a dose de 4800 mg/kg. Ratos tratados repetidamente com PA não apresentaram alterações significativas em parâmetros bioquímicos, hematológicos e histopatológicos, mas apresentaram sinais de irritabilidade e não mostraram ganho de massa corporal. A administração aguda de PA provocou danos no DNA (classe 4), determinados pelo ensaio cometa, em células do cérebro, fígado e sangue periférico. Os resultados obtidos para o extrato demonstram que PA administrado agudamente apresenta efeito hipnótico desprovido de efeito ansiolítico, sedativo ou comprometimento das funções motoras. Estes resultados podem explicar o efeito relatado pela população como agente indutor de sono, mas não apóiam o uso popular como calmante. Pelo contrário, o efeito ansiogênico e a toxicidade genética observados determinam à necessidade de cautela e a realização de mais estudos para a utilização de P. alata como matériaprima para a produção de medicamentos. / The aim of this work was to evaluate the toxicity and hypnotic/secative and anxiolytic effects of an aqueous spray-dried extract of P. alata (PA) (2.6% flavonoids), administrated by oral route, on barbiturate sleeping time, spontaneous locomotion, motor coordination, catalepsy induction, elevated plus-maze, pentilenotetrazole-induced convulsions and body temperature tests. In the acute treatment the doses ranged from 300 to 900 mg/kg; 300 mg/kg was used as repeated treatment. Genotoxicity was evaluated by ex vivo alkaline comet assay in mice (150, 300 and 600 mg/kg). PA 300 mg/kg decreased the latency and increased the barbiturate sleeping time. None of the tested doses of PA reduced spontaneous locomotion, induced catalepsy or performance deficit in rota-rod apparatus. Hypothermic effect was observed after administrating PA 300 and 600 mg/kg. The acute administration was not active on elevated plus-maze while repeated treatment (300 mg/kg) showed anxiogenic effect in this test. The acute (300 and 600 mg/kg) or repeated (300 mg/kg) administration of PA did not modify the number and severity of pentilenotetrazole-induced convulsions. In acute toxicity evaluation, mice deaths were not observed up to 4800 mg/kg. Rats repeatedly treated with aqueous extract did not present biochemical, hematological or histopathological significant alterations. However, the animals showed signs of irritability and did not increase body weight. In addition, mice acutely treated with PA presented DNA damage (class 4) determined by alkaline comet assay in brain, liver and peripheral blood cells. In conclusion, PA acute administration provokes hypnotic effect, destitute of anxiolytic and sedative effects and without concerning to motor functions. These results could explain the popular use as agent sleeping inductive, but they do not support the popular use, or commercialization, as tranquilizer/anxiolytic. On the contrary, the observed anxiogenic effect and genotoxicity request prudence and more studies in order to assure the efficacy and safety of utilization of P. alata with medicinal purposes.

O objetivo deste trabalho foi avaliar a toxicidade e ação hipnótico/sedativa e ansiolítica de um extrato seco nebulizado de Passiflora alata (PA) (2,6 % flavonóides totais), administrado pela via oral, nos testes de potenciação do sono barbitúrico, locomoção espontânea, coordenação motora, indução de catatonia, labirinto em cruz elevado, convulsões induzidas por pentilenotetrazol e temperatura corporal. PA foi administrado agudamente nas doses de 300, 600 e 900 mg/kg e por 14 dias, 300 mg/kg. Para avaliação da toxicidade aguda, foram empregadas doses de 600 a 4800 mg/kg. A genotoxicidade foi avaliada em camundongos (150, 300 e 600 mg/kg), pelo ensaio cometa alcalino. PA 300 mg/kg reduziu a latência e potenciou o tempo de sono barbitúrico. Em nenhuma das doses testadas, PA causou redução na locomoção espontânea, efeito catatônico ou prejuízos no desempenho em aparelho de rota-rod. O extrato (300 e 600 mg/kg) apresentou efeito hipotérmico. A administração aguda de PA não foi ativa no labirinto em cruz elevado e a administração repetida (300 mg/kg) provocou efeito ansiogênico. A administração aguda (300 e 600 mg/kg) ou repetida (300 mg/kg) de PA não alterou o número e a severidade das convulsões induzidas por pentilenotetrazol. Na avaliação da toxicidade aguda, não ocorreram mortes até a dose de 4800 mg/kg. Ratos tratados repetidamente com PA não apresentaram alterações significativas em parâmetros bioquímicos, hematológicos e histopatológicos, mas apresentaram sinais de irritabilidade e não mostraram ganho de massa corporal. A administração aguda de PA provocou danos no DNA (classe 4), determinados pelo ensaio cometa, em células do cérebro, fígado e sangue periférico. Os resultados obtidos para o extrato demonstram que PA administrado agudamente apresenta efeito hipnótico desprovido de efeito ansiolítico, sedativo ou comprometimento das funções motoras. Estes resultados podem explicar o efeito relatado pela população como agente indutor de sono, mas não apóiam o uso popular como calmante. Pelo contrário, o efeito ansiogênico e a toxicidade genética observados determinam à necessidade de cautela e a realização de mais estudos para a utilização de P. alata como matériaprima para a produção de medicamentos. / The aim of this work was to evaluate the toxicity and hypnotic/secative and anxiolytic effects of an aqueous spray-dried extract of P. alata (PA) (2.6% flavonoids), administrated by oral route, on barbiturate sleeping time, spontaneous locomotion, motor coordination, catalepsy induction, elevated plus-maze, pentilenotetrazole-induced convulsions and body temperature tests. In the acute treatment the doses ranged from 300 to 900 mg/kg; 300 mg/kg was used as repeated treatment. Genotoxicity was evaluated by ex vivo alkaline comet assay in mice (150, 300 and 600 mg/kg). PA 300 mg/kg decreased the latency and increased the barbiturate sleeping time. None of the tested doses of PA reduced spontaneous locomotion, induced catalepsy or performance deficit in rota-rod apparatus. Hypothermic effect was observed after administrating PA 300 and 600 mg/kg. The acute administration was not active on elevated plus-maze while repeated treatment (300 mg/kg) showed anxiogenic effect in this test. The acute (300 and 600 mg/kg) or repeated (300 mg/kg) administration of PA did not modify the number and severity of pentilenotetrazole-induced convulsions. In acute toxicity evaluation, mice deaths were not observed up to 4800 mg/kg. Rats repeatedly treated with aqueous extract did not present biochemical, hematological or histopathological significant alterations. However, the animals showed signs of irritability and did not increase body weight. In addition, mice acutely treated with PA presented DNA damage (class 4) determined by alkaline comet assay in brain, liver and peripheral blood cells. In conclusion, PA acute administration provokes hypnotic effect, destitute of anxiolytic and sedative effects and without concerning to motor functions. These results could explain the popular use as agent sleeping inductive, but they do not support the popular use, or commercialization, as tranquilizer/anxiolytic. On the contrary, the observed anxiogenic effect and genotoxicity request prudence and more studies in order to assure the efficacy and safety of utilization of P. alata with medicinal purposes.

Abstract Within the last few decades, electroencephalogram (EEG) has become a widely used tool for the automatic assessment of depth of anesthesia. The EEG-based depth of anesthesia measurement has been associated with several advantages, such as a decreased incidence of intraoperative awareness and recall, faster recovery, and reduced consumption of anesthetics. However, the measurement is challenged by simultaneous administration of different types of anesthetics, which is the common practice in the operating rooms today. Especially, the assessment of depth of anesthesia induced by supplementing the primary anesthetic drug, i.e. the hypnotic agent, with an opioid has been raised as one of the major problems in the field. In this thesis, the EEG-based depth of anesthesia measurement during multidrug infusion with propofol (hypnotic agent) and remifentanil (opioid) is addressed. The problem is approached by first giving a quantitative description for the EEG changes occurring during propofol infusion. Two different methods, both utilizing the spectral properties of EEG, for this are presented. Next, the effects of remifentanil on the clinical signs and EEG changes during propofol infusion are investigated by applying the first one of the presented methods. Coadministration of opioid is shown to significantly modify the mutual relations of the EEG changes and the clinical signs of the patient. Furthermore, remifentanil is found to significantly affect the EEG itself, more specifically, the power spectrum and derived quantitative parameters during propofol infusion. This effect is strongly dependent on the level of anesthesia. Finally, by utilizing the results on the effects of remifentanil, a technology is developed for the assessment of depth of propofol-remifentanil anesthesia. The technology is based on improving the determination of the anesthetic state of the patient by EEG-based separation of the effects of propofol and remifentanil. The thesis provides a framework for the depth of anesthesia measurement during multidrug administration with propofol and remifentanil. Due to the similar mechanisms of action, the results are likely to be generalizable to other hypnotic-opioid drug combinations. The study thus offers potential for the development of more advanced systems for automatic monitoring of depth of anesthesia. / Tiivistelmä Viime vuosikymmeninä elektroenkefalogrammista (EEG) on tullut suosittu apuväline anestesian syvyyden automaattisessa seurannassa. EEG-pohjaisella anestesian syvyyden mittauksella on saavutettu useita hyötyjä: sillä on pystytty esimerkiksi vähentämään leikkauksen aikaista hereillä oloa, pienentämään anesteettien kulutusta sekä nopeuttamaan anestesiasta palautumista. Mittaus on kuitenkin haasteellista yhdistelmäanestesiassa, jossa useampaa erityyppistä anesteettia käytetään samanaikaisesti. Erityisesti nykyisin yleisesti käytössä oleva tapa täydentää pääasiallista anesteettia eli hypnoottia opioidilla on nostettu yhdeksi merkittävimmistä haasteista automaattisessa anestesian syvyyden mittauksessa. Väitöskirja käsittelee EEG-pohjaista anestesian syvyyden mittausta käytettäessä propofolin (hypnootti) ja remifentaniilin (opioidi) yhdistelmää. Ongelmaa lähestytään antamalla aluksi kvantitatiivinen kuvaus propofoli-induktion aikana ilmeneville EEG-muutoksille. Tähän tarkoitukseen esitetään kaksi menetelmää, joista molemmat hyödyntävät EEG:n taajuussisältöä. Seuraavaksi remifentaniilin vaikutusta potilaan kliinisiin merkkeihin sekä EEG-muutoksiin propofoli-infuusion aikana tutkitaan soveltamalla ensimmäistä esitetyistä menetelmistä. Opioidin osoitetaan vaikuttavan merkittävästi EEG-muutosten ja kliinisten merkkien väliseen yhteyteen. Lisäksi remifentaniilin todetaan vaikuttavan merkittävästi myös propofoli-infuusion aikana ilmeneviin EEG-muutoksiin. Vaikutus heijastuu signaalin tehotiheysspektriin sekä siitä johdettuihin kvantitatiivisiin parametreihin ja on vahvasti riippuvainen anestesian syvyydestä. Lopuksi, hyödyntämällä tuloksia remifentaniilin vaikutuksista, esitetään teknologia propofoli-remifentanilli-yhdistelmäanestesian syvyyden mittaukseen. Teknologia perustuu propofolin ja remifentaniilin vaikutusten EEG-pohjaiseen erotteluun ja tätä hyödyntäen potilaan anestesian syvyyden tarkempaan määrittämiseen. Väitöskirja tarjoaa tarvittavan tutkimustiedon sekä teknologian propofoli-remifentanilli-yhdistelmäanestesian syvyyden mittaukseen. Samankaltaisten vaikutusmekanismien vuoksi tulokset on mahdollista yleistää myös muille hypnootti-opioidi-lääkeyhdistelmille. Tutkimus avaa näin uusia mahdollisuuksia kehittää edistyneempiä anestesian syvyyttä automaattisesti seuraavia järjestelmiä.

A total of 60 male and female subjects scoring between 0-5 and 8-12 on the Harvard Group Scale of Hypnotic Susceptibility: Form A underwent hypnosis procedures, hypnosis and age regression procedures to age 10, or were read an article about hypnosis. All subjects then listened to 20 minutes of directed imagery for warming and cooling the hands. Skin temperature was monitored on both index fingers. Dependent measures were the difference between each subject's highest temperature and baseline temperature, the difference between each subject's baseline temperature and lowest temperature, and the latency of change from baseline to highest temperature, and the latency of change from the beginning of cooling imagery to lowest temperature. Results indicated that the age regression group achieved significantly warmer temperatures than the control group and that the age regression group remained significantly warmer than the two other groups during the cooling imagery. Results also indicated that these skin temperature responses generalized to the nondominant hand. The data were interpreted as suggesting that those subjects exposed to the age regression procedures may have been more relaxed than the other groups. Another interpretation suggested the cooling imagery may not have been accessing common or pleasant experiences of the subjects.

The high prevalence of people affected by any anxiety disorder associated with the side effects of long-term pharmacotherapy has made possible and motivated the search for new therapies. As complementary and alternative therapy, tisanes obtained from leaves, bark and flowers of many species of the genus Citrus are used by the population in order to minimize emotional disorders and are recommended in the treatment of anxiety. Nocontexto the search for new compounds anti-anxiety drugs and hypnotic sedatives, the present study aimed to investigate the mechanism of action anxiolytic and hypnotic-sedative in vivo activity of essential oil of fruit rinds of Citrus limon (OECl). The experimental procedures were performed with the essential oil in the form in which it is marketed (Ferquima IND. e com. Ltda, São Paulo). Were used Swiss mice (n = 8), adults, males, weighing 25-35 g, from the Vivarium of the Federal University of Alagoas. Tests for potentiation of sleep induced by barbiturate-in order to evaluate its effect on sleep – besides the maze in high cross (LCE) and light and dark (CCE) agonists and antagonists using the tracks and/or Gabaergic neurotransmission-in order to evaluate the anxiolytic action mechanism; as well as the evaluation of a possible compromise engine, through the testing of rotary bar and catalepsy, were carried out in the laboratory of Pharmacology and immunity. The potentiation of sleep, oral treatment with OECl at a dose of 300 mg/kg decreased latency and increased the total time of sleep (p < 0.001). In experimental models of anxiety, the OECl (in doses of 100 and 300 mg/kg) induced an increase in the number of entries and the percentage of time in with open arms and, consequently, reduced the same parameters to the arms closed when compared to vehicle group in the ICE. In addition, these same doses increased the number of transitions and the percentage of time in the area clear in CCE, compared to the control group (p < 0.001). The anxiolytic action mechanism of OECl has been investigated through the pre-treatment with flumazenil, NAN-190 and ketanserin in same models of anxiety. The anxiolytic effect was antagonized by pretreatment with only flumazenil. In the evaluation of motor performance, there were no prejudice on motor function of animals in the testing of rotary bar and catalepsy. The results suggest that oral treatment with OECl induces a behavior anxiolytic in mice suggestively modulated by binding site on the GABAA receptor benzodiazepine or by increased Gabaergic transmission neuro, so there is no compromise of locomotive system. / Fundação de Amparo a Pesquisa do Estado de Alagoas / A alta prevalência de pessoas acometidas por algum distúrbio de ansiedade associada aos efeitos colaterais da farmacoterapia a longo prazo tem possibilitado e motivado a procura por novas terapias. Como terapia complementar e alternativa, infusos obtidos de folhas, cascas e flores de muitas espécies do gênero Citrus são utilizados pela população no sentido de minimizar distúrbios emocionais e são recomendados no tratamento da ansiedade. Nocontexto da busca por novos compostos ansiolíticos e hipnótico-sedativos, o presente estudo objetivou investigar o mecanismo de ação ansiolítico e a atividade hipnótico-sedativa in vivo do óleo essencial das cascas do fruto de Citrus limon (OECl). Os procedimentos experimentais foram realizados com o óleo essencial na forma em que é comercializado(Ferquima Ind. e Com. Ltda, São Paulo). Foram utilizados camundongos Swiss (n = 8), adultos, machos, pesando 25-35 g, provenientes do Biotério Central da Universidade Federal de Alagoas. Os testes de potencialização do sono induzido por barbitúrico – objetivando avaliar seu efeito sobre o sono – além do labirinto em cruz elevado (LCE) e a caixa claro e escuro (CCE), utilizando agonistas e antagonistas das vias GABAérgica e/ou serotoninérgica – a fim de se avaliar o mecanismo de ação ansiolítico; bem como a avaliação de um possível comprometimento motor, através dos testes da barra giratória e catalepsia, foram realizados no Laboratório de Farmacologia e Imunidade. No teste de potencialização do sono, o tratamento oral com OECl na dose de 300 mg/kg diminuiu a latência e aumentou o tempo total de sono (p < 0,001). Nos modelos experimentais de ansiedade, o OECl (nas doses de 100 e 300 mg/kg) induziu um aumento no número de entradas e na porcentagem de tempo nos braços abertos e, consequentemente, reduziu os mesmos parâmetros para os braços fechados quando comparado ao grupo veículo no LCE. Além disso, essas mesmas doses aumentaram o número de transições e a porcentagem de tempo na área clara na CCE, comparando-se ao mesmo grupo controle (p < 0,001). O mecanismo de ação ansiolítico do OECl foi investigado através do pré-tratamento com flumazenil, NAN-190 e ketanserina nos mesmos modelos de ansiedade. O efeito ansiolítico foi antagonizado apenas pelo pré-tratamento com flumazenil. Na avaliação da performance motora, não foi observado nenhum prejuízo na função motora dos animais nos testes da barra giratória e catalepsia. Os resultados sugerem que o tratamento oral com OECl induz um comportamento ansiolítico em camundongos sugestivamente modulado pelo sítio de ligação benzodiazepínico no receptor GABAA ou pelo aumento da neuro transmissão GABAérgica, de modo que não há comprometimento do aparelho locomotor.

In general, highly hypnotizable individuals ("highs") have exhibited greater abilities to focus attention and inhibit pain than low hypnotizable individuals ("lows"). Furthermore, highs appear to have faster neural processing than lows. The present study investigated differences between lows and highs in morphological volume of some brain structures associated with inhibitory and excitatory neural processing, particularly the corpus callosum (CC). Participants were 18 healthy university students, aged 18 to 29, with no history of concussion or medical disorders. They were in a functional Magnetic Resonance Image (fMRI) study examining the neurophysiology of pain and hypnotic analgesia (Crawford, Horton, Harrington, et al., 1998; Downs et al., 1998). As assessed by the group version (Crawford & Allen, 1982) of the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C; Weitzenhoffer & Hilgard, 1962), there were eight highs (four women and four men; SHSS:C M = 11.0) and 10 lows (five men and five women; SHSS:C M = 2.1). Highs were able to successfully eliminate perception of pain and distress to experimental noxious stimuli. Their anatomical MRIs were measured to assess relationships between brain structure volume (CC, medial cortex, anterior brain regions) and hypnotizability. In comparison to lows, highs had a significantly larger CC volume in the rostrum and isthmus, inferred to reflect larger transcallosal axon diameter or greater axon myelination. For highs, but not lows, there were significant relationships between forebrain volume and the total CC, rostrum, and splenium. Findings provide support for the neuropsychophysiological model of Crawford and her associates (e.g. Crawford, 1994a, 1994b; Crawford & Gruzelier, 1992) proposing a more effective attentional system of inhibitory processes in highs than lows. Furthermore, the data suggest that the more effective systems of attentional and inhibitory processes enhanced neural processing speed, and interhemispheric transfer times seen in highs than lows, may be associated with morphological differences in certain anterior and posterior CC regions. These regions are known to be involved in the allocation of inhibitory and excitatory transfer of information between hemispheres. / Ph. D.