A adicção a drogas caracteriza-se pelo recurso a uma substância, à qual se atribui o poder de funcionar como o único meio capaz de trazer alívio aos estados de angústia vividos internamente. Não há consenso com relação à reunião dos pacientes dependentes químicos em uma estrutura especificamente adictiva, mas o que se percebe é que, apesar de haver casos com funcionamentos diversos, naqueles em que as drogas assumem status de único caminho possível ao alívio do sofrimento interno, a dinâmica psíquica aproxima-se daquela exibida nos funcionamentos limites da personalidade. Assim, decidiu-se investigar a dinâmica psíquica de 20 jovens adictos a cocaína e/ou crack, pacientes de um CAPS ad II de um município da Grande São Paulo, por meio do Método de Rorschach, buscando identificar em que medida esta dinâmica assemelha-se à caracterização dos funcionamentos limites da personalidade, encontrada na literatura específica de orientação psicanalítica. Foi realizada uma análise qualitativa de cada um dos protocolos de Rorschach, segundo a estrutura proposta por Chabert (2000), em seu estudo sobre os funcionamentos limites da personalidade. Este estudo envolve a análise das modalidades de relação com o clínico; da representação de si; das representações de relações; e da organização defensiva. Realizou-se uma análise comparativa dos resultados do grupo em cada uma dessas categorias. Além disso, é exibida uma síntese do funcionamento psicodinâmico de cada paciente. Os dados revelam que a maior parte dos pacientes estudados exibe boa construção da imagem de si, mas com fronteiras ameaçadas por importantes cargas agressivas, sexuais e depressivas; intenso recurso ao determinante formal, com rebaixamento de sua qualidade; problemas nos processos de identificação secundária; tentativa de manejo dos afetos por meio da via intelectual, nem sempre bem sucedida; impossibilidade de contenção dos impulsos ligados à agressão; impulsividade; movimentos regressivos importantes; manifestação de dependência e de necessidade de apoio; prevalência dos mecanismos de defesa de idealização/desvalorização e de recusa parcial da realidade em nível profundo. Ou seja, a problemática aproxima-se daquela exibida nos funcionamentos limites de personalidade. A partir disso, propõe-se, em termos winnicottianos, que as instituições de tratamento possam fornecer o equilíbrio e a constância ambiental necessários à retomada do desenvolvimento emocional, permitindo que o paciente faça delas um uso transicional rumo à independência / The drug addiction is characterized through the use of a substance, to which the power of functioning as the only mean capable of bringing relief to the anguish states internally lived by an individual is attributed. There is no consensus regarding the gathering of chemically dependent patients in a specifically addictive structure, however, in spite of the existence of diversified performance cases, those in which the drugs assume a status of the only possible way to the internal suffering relief, the psychic dynamic approaches itself to the one exhibited in the personality limit states. Thus, a decision was made to investigate the psychic dynamic of 20 young people, addicted to cocaine and/or crack, patients of a CAPS ad II in a city belonging to the Great São Paulo, by means of the Rorschach Method, with the intent to identify in which measure this dynamic resembles the characterisation of the personality limit functioning, found in the specific literature of psychoanalytic orientation. A qualitative analysis of each one of the Rorschach protocols was performed, in accordance with the structure proposed by Chabert (2000), in his study about Borderline Personality. This study involves the analysis of the relations modalities with the clinician; of the self representation; of the relations representations; and of the defensive organization. A comparative analysis of the group results in each one of these categories was performed. Furthermore, a synthesis of the psychodynamic functioning of each patient is exhibited. Subject data reveal that the majority of the analysed patients exhibit a good self image construction, however with boundaries menaced through important aggressive contents, sexual and depressive; intensive expedient to the formal determinant, with diminishing effect in its quality; problems related to the secondary identification processes; tentative to handle affection through intellectual means, not always with success; impossibility to refrain impulses linked to aggression; impulsivity; important regressive moves; manifestation of dependency, as well as of support necessity; prevalence of the mechanisms of idealization/devaluation defence and of the partial reality refusal in profound levels. That is, the problematic approaches that one, exhibited in the limit functioning of personality. With this content in mind, it is proposed, in winnicottian terms, that the treatment institutions may provide the equilibrium and environmental constancy, necessary to the emotional development recovery, thus permitting the patient to make a transitional use of them, towards independency

Made available in DSpace on 2016-03-22T17:26:36Z (GMT). No. of bitstreams: 1 Dissert Rogerio Goncalves do Amaral.pdf: 234851 bytes, checksum: da3c002d659e5f365e9fe87b5421f59e (MD5) Previous issue date: 2011-06-22 / Objectives: Evaluate the profile and patterns of consumption of crack cocaine users who were hospitalized in Pelotas, Southern Brazil. Also, it was estimated the time to become addict, since the moment crack cocaine was used by the first time. . Methods: Cross-sectional study of 162 patients with the help of a structured questionnaire evaluating socio-demographic characteristics, strategies used to obtain the drug, ways of access to the drug, and criminal history. ICD-10 criteria were used to estimate the time between first use and addiction. Results: Most patients were young men (82,1%) with low literacy level and low income. The main strategy to obtain the drug was stealing, assaulting and drug traffic. The access to drugs was considered very easy (49,4%) or easy (42%) by most of the addicts, and 86% were able to obtain the drug in less than 30 minutes. After two months of having used crack for the first time, 44% were addicts, and this proportion increased to 73% with six months of use and 87% after one year. Conclusions: Crack cocaine is very easy to obtain and it leads to addiction in a short period of time. As it is widely used, and criminal acts are commonly used for its achievement, crack cocaine is an important reason for the increase of violence in urban societies / Objetivos: Estudar o perfil e padrões de consumo de pacientes internados por uso de crack, e estimar o tempo para se tornar dependente após experimentar crack pela primeira vez. Métodos: Estudo transversal com 162 pacientes internados para desintoxicação em um hospital psiquiátrico em Pelotas, Rio Grande do Sul. Utilizou-se um questionário para avaliar características sociodemográficas, estratégias usadas para adquirir crack, acesso à droga e história penitenciária criminal. Os critérios da CID-10 para síndrome de dependência foram usados para estimar o tempo em que o paciente se tornou dependente após experimentar a primeira pedra de crack. Resultados: A maioria dos pacientes era homens jovens (82,1%), com baixa escolaridade e renda. A principal estratégia ilegal para conseguir crack foi furtar, seguida por assaltos e tráfico de drogas. O acesso à droga foi considerado muito fácil (49,4%) ou fácil (42%) pela maioria dos usuários, sendo que 86% tinham acesso ao crack em menos de 30 minutos. Dois meses após experimentarem a primeira pedra de crack, 44% já se tornaram dependentes, e esta proporção aumentou para 73% aos seis meses e 87% com um ano. Conclusões: O crack é uma substância com acesso muito fácil que leva a dependência em período muito curto e com um impacto importante no aumento da violência na sociedade

A compulsão à repetição é um conceito fundamental na obra de Freud. Em nosso atual estado da arte, ela está relacionada, mais diretamente, com determinados quadros clínicos, como a toxicomania. Assim, o objetivo deste trabalho é identificar e discutir as manifestações clínicas da compulsão à repetição: 1) em sua relação com as resistências, em especial com a reação terapêutica negativa; e 2) sua incidência no quadro psicopatológico da toxicomania. Trata-se de um estudo teórico, realizado com o método psicanalítico histórico-crítico de leitura. Foram utilizadas três categorias de análise textual: 1) identificação do tema central e dos temas periféricos; 2) identificação das possíveis contradições, esquecimentos, lacunas argumentativas, repetições e elementos intertextuais; e 3) identificação e contextualização dos diferentes usos que esse conceito tem em cada texto. Constatou-se que, em Freud, existem momentos centrais de análise desse conceito: a) postulação, em 1914, em Recordar, repetir e elaborar. Nessa situação, ela estava circunscrita ao princípio de prazer; b) situada Além do princípio de prazer (1920) e como fenômeno de base para hipótese das pulsões de morte; e c) como resistência do Id, em Inibição, sintoma e angústia (1926). A compulsão à repetição, em conjunto com a necessidade de punição originada no Superego, forma um bloco resistencial maciço, que pode ser identificado na reação terapêutica negativa. Para tanto, utiliza-se de outros tipos de resistências, tais como a transferência, o ganho secundário da neurose e o recalque. Na toxicomania, a acentuada incidência desse fenômeno repetitivo estaria relacionada com o excesso de impulsos em estado bruto, não ligados, assim como uma tendência a descarregá-los por meio de atuações. O prazer encontrado na droga encobriria, em última instância, o trabalho silencioso das pulsões de morte. Haveria uma estreita e complicada articulação entre prazer e desprazer; ausência/presença e falta. Se, por um lado, é importante não esquecermos a repetição do mesmo e os efeitos destrutivos da droga; por outro, é necessário nos lembrarmos de como a droga pode ser utilizada como uma espécie de medicação, para o enfrentamento do sofrimento psíquico. Nesse sentido, ela poderia indicar uma busca irrefreável por ligação (Bindung) e religação / The compulsion for repetition is a fundamental concept in the work of Freud. In our current state of art, it is related more directly to specific clinical pictures, such as drug addiction. Thus, the objective of this work is to identify and discuss the clinical manifestations of compulsion for repetition: 1) in its relation to the resistances, specially with the negative therapeutic reaction; 2) its incidence in the psychopathologic picture of drug addiction. It\'s a theoretical study, accomplished with the historical-critical psychoanalytic method of reading. Three categories of textual analysis were used: 1) identification of the central theme and of the peripheral themes; 2) identification of possible contradictions, forgetfulness, argumentative gaps, repetitions and intertextual elements; and 3) identification and contextualization of the different uses this concept has in each text. It was verified that, in Freud, there are central moments of analysis of compulsion for repetition: a) postulation, in 1914, in Recollecting, repeating and working -through. In this situation, it was circumscribed to the principle of pleasure; b) situated Beyond the pleasure principle (1920) and as base phenomenon for the death drives hypothesis; and c) as resistance of Id, in Inhibition, symptoms and anxiety (1926). The compulsion for repetition, together with the need of punishment originated in the Superego, forms a solid block of resistance that can be identified in the negative therapeutic reaction. Thereunto, other types of resistance are used, such as transference, the secondary gain of neurosis and the repression. In drug addiction, the accentuated incidence of this repetitive phenomenon would be related to the excess of impulses in a raw form, not connected, as well as a tendency to unload them through actions. The pleasure found in drugs would ultimately cover the silent work of death drives. There would be a close and complicated articulation between pleasure and displeasure; absence and presence. If, on the one hand, it is important not to forget the repetition and the destructive effects of drugs, on the other hand it is necessary to remember how drugs can be utilized as a type of medication for the confrontation of the psychic suffering. In this way, they could indicate an unrestrainable search for connection (Bindung) and reconnection

Made available in DSpace on 2016-04-29T14:16:46Z (GMT). No. of bitstreams: 1 Denis Barreto da Silva.pdf: 2962209 bytes, checksum: 9b679017ca245a43c3633333f07013df (MD5) Previous issue date: 2015-09-16 / This work aimed to investigate the intervention of Social Work in process of social reintegration of persons in situation of abusive use and / or drug addiction. The field research was conducted in a therapeutic community in the municipality of Itapecerica da Serra São Paulo, Brazil, in an institution for abusive wearers and drug addicts in the city of Grenoble, France. The field research in France took place from our participation in the double degree program signed by PUC-SP and UPMF-Grenoble / France. The starting point for this analysis consisted in a qualitative study using three methods in coordination. They were: participant observation, case study and actionresearch. The instruments used were: group discussion, in-depth interviews and home visits applied to the research. As a result of this process, some empirical categories emerged, such as drug; the relationship with the family and the community; the look of the subjects on Social Work; the relationship between the exclusion and drug addiction, among others. The study revealed that although there is a need for coordination between the different services and approaches in the sphere of drugs care, which prevails in Brazil is a dynamic competitiveness between the various approaches. The survey also showed that within an interdisciplinary dynamic, the intervention of Social Work emerges with relevance, assessed on a perspective that considers the role of the subject in the reintegration process / O presente trabalho teve como proposta investigar a intervenção do Serviço Social no processo de reinserção social de pessoas em situação de uso abusivo e/ou dependente de drogas. A pesquisa de campo foi realizada em uma Comunidade Terapêutica no município de Itapecerica da Serra-SP, em uma instituição destinada ao atendimento de usuários abusivos e dependentes de drogas na cidade de Grenoble, na França. A pesquisa de campo em território francês realizou-se a partir de nossa participação no programa de dupla titulação firmado entre a PUC-SP e a UPMF-Grenoble/França. O ponto de partida para essa análise consistiu-se em uma pesquisa de caráter qualitativo, utilizando três métodos de forma articulada. Foram eles: a observação participante, o estudo de caso e a pesquisa-ação. Sendo que os instrumentos empregados foram: grupo de discussão, entrevista em profundidade e visitas domiciliares aplicadas a pesquisa. Como resultado deste processo, algumas categorias empíricas emergiram, tais como: a droga; a relação com a família e com a comunidade; o olhar dos sujeitos sobre o Serviço Social; a relação entre a exclusão e a dependência de drogas, dentre outras. O estudo revelou que apesar de haver a necessidade de articulação entre os diferentes serviços e abordagens na esfera da atenção as drogas, o que prevalece no Brasil é uma dinâmica de concorrencialismo entre as diversas abordagens. A pesquisa demonstrou ainda que dentro de uma dinâmica interdisciplinar, a intervenção do Serviço Social desponta com relevância, apreciada numa perspectiva que considera o protagonismo do sujeito no processo de reinserção

A farmacodependência é considerada uma doença crônica e sujeita à recaídas, na qual o indivíduo perde o controle sob a utilização de determinada droga de abuso. Conforme o usuário persiste com o uso da droga, ocorrem alterações anatômicas, fisiológicas e neuroquímicas no sistema nervoso central (SNC), as quais podem culminar no desenvolvimento de um comportamento compulsivo. A neurobiologia deste processo é complexa e envolve mecanismos de plasticidade em diferentes sistemas neurotransmissores. O principal deles é o sistema mesocorticolímbico dopaminérgico, constituído por neurônios da área ventral do tegmento mesencefálico (VTA) que se projetam para o núcleo accumbens (NAc) e ao córtex pré-frontal (CPF), diretamente relacionado aos processos motivação e recompensa. Contudo, o mesmo não é suficiente para elucidar a complexidade da doença, o que levou ao entendimento da presença de outros sistemas neurotransmissores neste processo. Sabe-se que o sistema colinérgico muscarínico está diretamente envolvido em diferentes doenças neuropsiquiátricas, incluindo a farmacodependência. Além disso, os receptores colinérgicos muscarínicos (mAChRs) estão densamente presentes em regiões límbicas, onde acetilcolina e dopamina interagem por neuromodulação. Diante disto, o objetivo deste trabalho foi investigar as possíveis alterações plásticas no sistema colinérgico muscarínico resultantes de tratamentos com cocaína que mimetizaram o consumo compulsivo humano. Para tanto, foram realizados ensaios comportamentais com camundongos Swiss machos adultos em campo aberto, tratados durante um (acute binge paradigm, 30 mg/kg) ou 14 dias (escalating dose binge paradigm, 15 - 30 mg/kg) com cocaína. Os animais receberam 3 injeções intraperitoneais (i.p.) de cocaína com intervalos de 60 minutos, durante os quais a atividade locomotora foi avaliada. Após a análise comportamental, os animais foram eutanasiados por decapitação para a remoção do encéfalo e dissecação do estriado, CPF e hipocampo, regiões cerebrais cruciais para o processo fisiopatológico da farmacodependência. Componentes do sistema dopaminérgico (receptores D1 e D2) e colinérgico muscarínico (M1-M5 mAChRs, ChAT, VAChT e AChE) foram avaliados por Immunoblotting. O sangue dos animais foi coletado para a realização das dosagens de cocaína e benzoeilecgonidina por UPLC-MS/MS. O desempenho locomotor total dos animais tratados com cocaína foi superior ao dos animais controle. O grupo tratado com escalonamento de dose desenvolveu sensibilização comportamental aos efeitos psicoestimulantes da cocaína no segundo dia de tratamento e, a partir dele, a atividade locomotora total manteve a mesma magnitude. Além disso, conforme o aumento da dose, os animais mantiveram um nível de atividade superior ao basal, mesmo após o término do experimento. As análises de Immunoblotting mostraram alterações dopaminérgicas e colinérgicas. No estriado observou-se redução da densidade de D2R após o tratamento de 14 dias e aumento na densidade de M3 mAChR após o tratamento agudo. Já no hipocampo observou-se redução de D1R e aumento de D2R, M1 e M5 mAChR após o tratamento crônico; e um aumento na densidade de M3 mAChR após o tratamento agudo. No CPF, foi evidenciada redução de M3 e de M5 mAChR após o tratamento cônico de 14 dias. Em relação às moléculas colinérgicas, observou-se, após o tratamento crônico, aumento da quantidade de ChAT em todas as estruturas estudadas. Além disso, VAChT mostrou-se aumentado no hipocampo após ambos os tratamentos. As dosagens plasmáticas revelaram a presença de 20,38 ± 3,4 ng/mL de cocaína e 224,6 ± 24,02 ng/mL de benzoilcgonina (BZE) nos animais do grupo agudo e, nos do grupo crônico, 62,26 ± 10,56 ng/mL e 375,1 ± 25,62 ng/mL de cocaína e BZE respectivamente. / Drug addiction is a chronic releapsing disorder characterized by the loss of control in limiting drug intake. As the drug use persists, anatomical, physiological and neurochemical changes occur in the central nervous system (CNS), which may lead to the development of compulsive behaviors. The neurobiology of this process is complex and involves mechanisms of plasticity in different neurotransmitter systems. The main one is the mesocorticolimbic dopaminergic system, composed by neurons from the ventral tegmental area (VTA) that projects to the nucleus accumbens (NAc), which is directly related to motivation and reward processes. However, just dopamine is not enough to elucidate the complexity of the disease, leading to the comprehension of another neurotransmitters system involved. It is known that the cholinergic system is involved in different neuropsychiatric disorders, including drug addiction. Furthermore, cholinergic muscarinic receptors (mAChRs) are densely present in limbic regions, where acetylcholine and dopamine interact by neuromodulation. Considering that, the aim of this study was to evaluate the existence of neuroadaptative changes in the cholinergic muscarinic system induced by cocaine in a compulsive-like behavior model in mice. Swiss-Webster adult male mice received 3 daily injections (i.p) of cocaine or saline, with a 60-min interval among them, either acutely (acute binge paradigm) or for 14 consecutive days (escalating dose binge paradigm). The locomotor activity was monitored in the open field during 60 min, in 5 min bins, after each injection. After behavioral analysis animals were euthanized by decapitation and the brain regions of striatum, hippocampus and prefrontal cortex, involved in the pathophysiology of addiction were dissected. Dopaminergic receptors (D1R and D2R), cholinergic muscarinic receptors (M1-M5 mAChRs), choline acetylytransferase (ChAT), acetylcholine vesicular transporter and acetylcholinesterase (AChE) were quantified by Immunoblotting. Blood samples were collected with heparin and plasma was separated and stored with 2% sodium fluorite at -80ºC for cocaine and benzoilecgonine quantification by UPLC-MS/MS. In the open field, animals treated with cocaine showed an increase in locomotor activity compared to control. Cocaine induced behavioral sensitization, in the escalating dose group on day 2, and after that the locomotor activity had the same magnitude until day 14th. These animals also kept the locomotor activity elevated even after the last injection. Immunobltting shows dopaminergic and cholinergic changes. An increase in M3 was observed in both hippocampus and striatum of animals acutely treated. After 14 days, there was an increase in M1, M5 and D2 and a decrease in D1 in hippocampus. There was also a decrease in D2 in the striatum; and finally, there was a decrease in M5 and M3 in the prefrontal cortex. ChAT densities were higher in all regions after the chronic treatment. Besides that, VAChT were higher in the hippocampus after both acute and chronic treatments. UPLC-MS/MS for cocaine and benzoilecgonine demonstrated the presence of 20,38 ± 3,4 ng/mL of cocaine and 224,6 ± 24,02 ng/mL of BZE in the acute binge group; and, 62,26 ± 10,56 ng/mL and 375,1 ± 25,62 ng/mL of cocaine and BZE, respectively in the escalating dose animals.

A adicção a drogas caracteriza-se pelo recurso a uma substância, à qual se atribui o poder de funcionar como o único meio capaz de trazer alívio aos estados de angústia vividos internamente. Não há consenso com relação à reunião dos pacientes dependentes químicos em uma estrutura especificamente adictiva, mas o que se percebe é que, apesar de haver casos com funcionamentos diversos, naqueles em que as drogas assumem status de único caminho possível ao alívio do sofrimento interno, a dinâmica psíquica aproxima-se daquela exibida nos funcionamentos limites da personalidade. Assim, decidiu-se investigar a dinâmica psíquica de 20 jovens adictos a cocaína e/ou crack, pacientes de um CAPS ad II de um município da Grande São Paulo, por meio do Método de Rorschach, buscando identificar em que medida esta dinâmica assemelha-se à caracterização dos funcionamentos limites da personalidade, encontrada na literatura específica de orientação psicanalítica. Foi realizada uma análise qualitativa de cada um dos protocolos de Rorschach, segundo a estrutura proposta por Chabert (2000), em seu estudo sobre os funcionamentos limites da personalidade. Este estudo envolve a análise das modalidades de relação com o clínico; da representação de si; das representações de relações; e da organização defensiva. Realizou-se uma análise comparativa dos resultados do grupo em cada uma dessas categorias. Além disso, é exibida uma síntese do funcionamento psicodinâmico de cada paciente. Os dados revelam que a maior parte dos pacientes estudados exibe boa construção da imagem de si, mas com fronteiras ameaçadas por importantes cargas agressivas, sexuais e depressivas; intenso recurso ao determinante formal, com rebaixamento de sua qualidade; problemas nos processos de identificação secundária; tentativa de manejo dos afetos por meio da via intelectual, nem sempre bem sucedida; impossibilidade de contenção dos impulsos ligados à agressão; impulsividade; movimentos regressivos importantes; manifestação de dependência e de necessidade de apoio; prevalência dos mecanismos de defesa de idealização/desvalorização e de recusa parcial da realidade em nível profundo. Ou seja, a problemática aproxima-se daquela exibida nos funcionamentos limites de personalidade. A partir disso, propõe-se, em termos winnicottianos, que as instituições de tratamento possam fornecer o equilíbrio e a constância ambiental necessários à retomada do desenvolvimento emocional, permitindo que o paciente faça delas um uso transicional rumo à independência / The drug addiction is characterized through the use of a substance, to which the power of functioning as the only mean capable of bringing relief to the anguish states internally lived by an individual is attributed. There is no consensus regarding the gathering of chemically dependent patients in a specifically addictive structure, however, in spite of the existence of diversified performance cases, those in which the drugs assume a status of the only possible way to the internal suffering relief, the psychic dynamic approaches itself to the one exhibited in the personality limit states. Thus, a decision was made to investigate the psychic dynamic of 20 young people, addicted to cocaine and/or crack, patients of a CAPS ad II in a city belonging to the Great São Paulo, by means of the Rorschach Method, with the intent to identify in which measure this dynamic resembles the characterisation of the personality limit functioning, found in the specific literature of psychoanalytic orientation. A qualitative analysis of each one of the Rorschach protocols was performed, in accordance with the structure proposed by Chabert (2000), in his study about Borderline Personality. This study involves the analysis of the relations modalities with the clinician; of the self representation; of the relations representations; and of the defensive organization. A comparative analysis of the group results in each one of these categories was performed. Furthermore, a synthesis of the psychodynamic functioning of each patient is exhibited. Subject data reveal that the majority of the analysed patients exhibit a good self image construction, however with boundaries menaced through important aggressive contents, sexual and depressive; intensive expedient to the formal determinant, with diminishing effect in its quality; problems related to the secondary identification processes; tentative to handle affection through intellectual means, not always with success; impossibility to refrain impulses linked to aggression; impulsivity; important regressive moves; manifestation of dependency, as well as of support necessity; prevalence of the mechanisms of idealization/devaluation defence and of the partial reality refusal in profound levels. That is, the problematic approaches that one, exhibited in the limit functioning of personality. With this content in mind, it is proposed, in winnicottian terms, that the treatment institutions may provide the equilibrium and environmental constancy, necessary to the emotional development recovery, thus permitting the patient to make a transitional use of them, towards independency

This highly readable introduction to the science of pharmacology assumes only a modest understanding of biology, chemistry, and human physiology. Author Peter J. Rice provides readers with a survey of the scientific understanding of drug action. He discusses pharmacology at a basic scientific level to build a framework of how drugs work, and he supplements this discussion with information on some representative drugs that are used clinically. KEY FEATURES: Concise and systematic introduction to the science of pharmacology; Knowledge objectives in each chapter; Glossary of key terms in each chapter; Review questions in each chapter with answers provided in the back of the book; Tables listing brand and generic drug names and dosage forms by drug class; More than 170 illustrations that supplement the text. / https://dc.etsu.edu/etsu_books/1033/thumbnail.jpg

Where We Belong is more than a memoir. It is a love story about the untimely death of the oldest of five daughters born to a prominent New Haven, Connecticut family. It is also a tale of hubris, rage and frustration, a Greek tragedy about a man's life as re-examined through the lens of the two weeks his wife spent dying, a tale in which chronic illness and good intentions ensure the death of a loving wife, artist and mother. The journey on which her husband takes the reader explores a health care system oblivious to her plight, her family's unwitting complicity and a 12-step mythology that unfolds while he, her six weeping children and her aging mother helplessly look on. The author endures an agony that dwarfs incentives to lie, learning that people lie out of fear, and genuine grief supplants fear with the stark reality of what we fear most: death. Where We Belong gives voice to the internal dialogue the author encounters when reexamining not just memories, but the accoutrements of memory, as well. It is a voice that addresses his own grandiosity, sentimentalism and self-pity in the face of his wife's death, in addition to those details, circumstances and impressions that speak to the arrogance he brought to the task of being all he thought she and her six children needed him to be. He concludes the task was well beyond him, a realization evoked by the gut wrenching decision to literally "pull the plug" on this heartbreaking tale of reconstituted hope and great promise reduced to rubble by chronic illness, alcoholism, drug addiction and death. Born is the lesson that when we grieve, we are free to be ourselves. When we are free to be ourselves, we are free to love again.

Acid-sensing ion channel 1A (ASIC1A) is abundant in the nucleus accumbens (NAc), a region known for its role in addiction. Because ASIC1A has been previously suggested to promote associative learning, we hypothesized that disrupting ASIC1A in the NAc would reduce drug-associated learning and memory. However, contrary to this hypothesis, we found that disrupting ASIC1A in the NAc increased cocaine-conditioned place preference, suggesting an unexpected role for ASIC1A in addiction-related behavior. Investigating the underlying mechanisms, we identified a novel postsynaptic current during neurotransmission mediated by ASIC1A and ASIC2 and thus well-positioned to regulate synapse structure and function. Consistent with this possibility, disrupting ASIC1A altered dendritic spine density and glutamate receptor function, and increased cocaine-evoked plasticity in AMPA-to-NMDA ratio, all resembling changes previously associated with cocaine-induced behavior. Together, these data suggest ASIC1A inhibits plasticity underlying addiction-related behavior, and raise the possibility of therapies for drug addiction by targeting ASIC-dependent neurotransmission. The amygdala plays critical roles in the learning and expression of fear-related behavior. Previous studies have implicated the amygdala in CO2-evoked fear-like behavior in mice; however, a more recent study demonstrated that humans lacking the amygdala bilaterally experience fear and panic with CO2-inhalation. Because all subjects lacking the amygdala had panic attacks after inhaling CO2 compared to only 25% of controls, this data suggests the amygdala may play an inhibitory role in CO2-evoked panic. To assess the role of the amygdala in CO2-evoked behaviors in mice, we lesioned the amygdala and optogenetically stimulated different amygdalar nuclei. We found that large unilateral and bilateral amygdala lesions caused the emergence of escape-like jumping behavior in mice exposed to CO2 and a relative deficit in CO2-evoked freezing. This jumping behavior depended on the dorsal periaqueductal gray, a brain area previously associated with panic attacks. Additionally, the putative CO2 chemosensor ASIC1A and ASIC2 are not necessary for CO2-evoked jumping, and may even play an inhibitory role in this behavior. Optogenetic manipulation of the amygdala revealed that stimulation of the basolateral amygdala enhanced jumping behavior and inhibited freezing behavior. This may be due to the basolateral amygdala's ability to inhibit the main output center of the amygdala, the central nucleus. Together, these results suggest that different amygdalar nuclei differentially modulate CO2-evoked behavior by regulating the switch between mobile and immobile defense responses. Additionally, they provide additional evidence that amygdalar dysfunction may contribute to panic disorder.

Studying protein-protein interactions has been vital for understanding how proteins function within the cell, how biological processes are strictly regulated by these interactions, and what molecular mechanisms underlie cellular functions and diseases. Recent biochemical and biophysical studies have provided evidence supporting that G protein-coupled receptors (GPCRs) can and do interact with one another to form dimers or larger oligomeric complexes, which may determine the structure and function of GPCRs, including receptor trafficking, scaffolding and signaling. This may help to understand the physiological roles of GPCRs and mechanisms underlying certain disease pathologies and to provide an alternative approach for drug intervention.<p>Cannabinoid CB1 and dopamine D2 receptors are the most common GPCRs in the brain and exert a mutual regulation in brain functions involved in learning, memory and drug addiction. There is structural and functional evidence supporting the idea that CB1 and D2 receptors physically interact with each other in hippocampal and striatal neurons to modulate their functions. Direct evidence supporting a physical interaction between the CB1 and D2 receptors was obtained from cultured HEK293 cells stably coexpressed with both receptors.<p> This research project was designed to critically test the hypothesis that a specific protein sequence (i.e. motif) in the D2 receptor is responsible for in vitro protein-protein interactions between the CB1 and D2 receptors. To reach this goal, fusion proteins containing various domains and motifs of the CB1 and D2 receptors were prepared and then used first to determine the domains of the CB1 and D2 receptors responsible for in vitro protein-protein interactions between CB1 and D2 receptors, and then to identify the specific motifs in the D2 receptor responsible for in vitro CB1 coupling with the D2 receptors. The major method used in this study is in vitro pull-down assay, which uses a purified and tagged bait protein to generate a specific affinity support that is able to bind and purify a prey protein from a lysate sample. The present study provides the first evidence that CB1 intracellular C-terminal (CB1-CT) and D2 intracellular loop 3 (D2-IL3) can directly interact with each other, and that the specific motifs D2-IL3(Ⅳ1) and D2-IL3(Ⅳ3) in the D2 receptor are likely responsible for their in vitro coupling with the CB1 receptors. <p>The results of the present study are invaluable for future research exploring in vivo protein-protein interaction between the CB1 and D2 receptors in the rat striatum by co-immunoprecipitation. Specifically, future studies will determine whether the identified specific motifs D2-IL3(Ⅳ1) and D2-IL3(Ⅳ3) in the D2 receptor are indeed critical for their in vivo coupling with the CB1 receptors.