Tendo em vista a imprevisibilidade da estabilidade oclusal pós correção ortodôntica, este estudo objetivou correlacionar a recidiva da sobremordida e da sobressaliência com a recidiva do apinhamento ântero-superior e ântero-inferior, em casos com má oclusão de Classe I e Classe II de Angle, tratados ortodonticamente com extração de 4 pré-molares, tratados pela técnica Edgewise. Para isso, foram selecionados 40 pacientes (20 do gênero feminino e 20 do gênero masculino), 25 pacientes portadores de má oclusão de Classe I e 15 de Classe II de Angle, com idade média inicial de 13,01 anos, que foram tratados por um tempo médio de 2,15 anos, e avaliados na fase pós-contenção após um período médio de 5,43 anos. Todos os pacientes apresentavam pelo menos 3 mm de sobremordida e 4mm de sobressaliência ao início do tratamento ortodôntico. Foram utilizados os modelos de gesso das fases do início do tratamento (T1), final de tratamento (T2) e da fase pós-contenção, em média 5 anos após o término do tratamento (T3) de todos os casos selecionados para que fossem quantificadas as recidivas dessas duas variáveis, assim como a recidiva do apinhamento anterior. Utilizou-se a análise de variância a um critério de seleção, e em caso de resultado significante, o teste de Tukey, para comparação intragrupos dos 3 tempos avaliados. Para verificação da presença de correlação entre a recidiva da sobressaliência e da sobremordida, com o apinhamento anterior, utilizou-se o teste de correlação de Pearson. A comparação intergrupos foi realizada por meio do teste t independente. Os resultados mostraram que houve uma correção significante do trespasse horizontal, vertical e apinhamento com o tratamento. Não houve uma recidiva significante do trespasse horizontal, vertical e do apinhamento ântero-superior no período pós-contenção, ao contrário do apinhamento ântero-inferior, que apresentou uma recidiva significante. Houve correlação significante da recidiva do trespasse horizontal com a recidiva do trespasse vertical. Não houve correlação significante entre a recidiva do trespasse horizontal e a recidiva do apinhamento anterior. Não houve correlação entre a recidiva do trespasse vertical e a recidiva do apinhamento anterior, assim como também não houve correlação entre a recidiva do apinhamento ântero-inferior e ântero-superior. Houve diferença intergrupos apenas para o apinhamento ântero-inferior ao início do tratamento, que foi maior no grupo Classe I, que apresentou também uma maior correção com o tratamento e um maior apinhamento na fase pós-contenção. / Due to the unpredictability of the occlusal stability after orthodontic correction, this study aimed to correlate the relapse of overbite and overjet with the relapse of maxillary and mandibular anterior crowding, in cases of Class I and Class II malocclusions, treated orthodontically with four premolars extraction and Edgewise technique. For this, 40 patients were selected (20 females and 20 males), 25 patients with Class I malocclusion and 15 with Class II, with initial age of 13.01 years, which were treated for a mean period of 2.15 years, and evaluated postretention after a mean period of 5.43 years. All patients had at least 3mm of overbite and 4mm of overjet at the beginning of orthodontic treatment. The dental casts from pretreatment (T1), posttreatment (T2) and postretention, on average 5 years after completion of treatment (T3), were used. It was used the one-way ANOVA, and in case of a significant result, Tukey\'s tests were used for intragroup comparison of the three times evaluated. To verify the presence of correlation between the relapse of overjet and overbite, with the relapse of anterior crowding, the Pearsons correlation test was used. Intergroup comparison was performed with independent t tests. The results showed a significant correction of the overjet, overbite and crowding during treatment. There was not a significant postretention relapse of overjet, overbite and crowding of the maxillary anterior segment, unlike the mandibular anterior crowding, which presented a significant relapse. There was a significant correlation of relapse of the overjet with the relapse of the overbite. No significant correlation between relapse of overjet and relapse of anterior crowding. There was no correlation between relapse of the overbite and relapse of anterior crowding, and there was also no correlation between mandibular anterior crowding relapse and maxillary anterior crowding relapse. There were differences between groups only for the mandibular crowding at pretreatment, which was higher in Class I, which also showed a larger correction with treatment and greater relapse of this crowding in the postretention.

Made available in DSpace on 2016-08-10T10:53:44Z (GMT). No. of bitstreams: 1 NEUSA MARIA BROCH COELHO.pdf: 890026 bytes, checksum: 9f03f843438e0b0b4712f59a48d1daf9 (MD5) Previous issue date: 2013-03-11 / Introduction: Rondonópolis is a municipality showing high endemicity for leprosy, however, with low relapse rates. No studies that address the causes of maintenance of high detection rates or effectiveness of multidrug therapy. Thus, the revision of data on leprosy diagnosed and all relapses may help in understanding the causes for maintenance of the endemic and improve actions towards control of the disease. Objectives: To characterize the leprosy relapse cases diagnosed between 1994 and 2010 in Rondonópolis-MT, who had been released from treatment. Material and Methods: We selected and evaluated the clinical records of all leprosy patients diagnosed and treated between 2000 and 2008, upon registration in the Health Reference Unit for leprosy of Rondonópolis and in the National Notifiable Disease System (SINAN, Ministry of Health). For the periods between 1994 and 1999, and from 2009 to 2010, we selected only the records of cases that had more than one entry in the system. The records were reviewed for clinical, laboratory and treatment scheme data collection, and these were transcribed to specific forms. Data was analyzed using descriptive statistics. Results: A total of 1863 records were evaluated (92.6% adults and 7.4% children under age 15 years), mean age was 38 years, 818 individuals had been treated with paucibacillary scheme, 886 with multibacillary and 158 with other therapeutic regimens, also 585 (31.4%) individuals had an episode of type 1 or type 2 reaction. The average bacilloscopic index (IB) of histological sections was 1.62. From the total, 151 individuals showed reactivation of leprosy, 27.1% had been treated with MDT / PB, 20.5% with MDT / MB and 52.3% with other schemes. Twenty four out of 41 individuals who were treated with PB scheme, only 8 were true relapses, 16 reactivated as MB and 17 MB took drugs irregularly. Among 31 individuals treated with MB scheme, 16 relapsed and 8 took drugs irregularly. The real percentage of relapses is 1.28% in the period. Conclusion: Patients showed a low percentage of relapses, probably due to the high efficacy of MDT, however, this was not sufficient to control the disease in the municipality of Rondonópolis. The bacterial persistence may have significant role in the relapse, since one would expect greater number of relapses associated with reinfection in a highly endemic area. Therefore, despite the referral service being well structured, it is not enough to cover the current demand on diagnostic tests for leprosy and evaluation of contacts for disease control. / Introdução: Rondonópolis é um município de alta endemicidade para hanseníase, no entanto, com baixas taxas de recidiva. Não estudos que enfoquem as causas de manutenção de altas taxas de detecção ou eficácia da poliquimioterapia. Deste modo, a revisão de dados sobre casos de hanseníase diagnosticados e todas as recidivas pode auxiliar no entendimento das causas de manutenção da endemia e melhorar as ações de controle da doença. Objetivos: Caracterizar os casos de recidiva de hanseníase diagnosticados entre 1994 e 2010 em Rondonópolis-MT que tiveram alta por cura, quanto às características clínico-laboratoriais, epidemiológicas e terapêuticas. Material e Métodos: Foram selecionados e avaliados todos os prontuários de pacientes de hanseníase diagnosticados e tratados entre os anos 2000 e 2008, mediante registro na Unidade de Referência no município de Rondonópolis e no sistema nacional de agravos de notificação SINAN Ministério da Saúde). Para os períodos de 1994 a 1999, e 2009 a 2010, foram selecionados somente os prontuários de casos que tiveram mais de uma entrada no sistema. Os prontuários foram examinados para coleta de dados clínicos, laboratoriais e terapêuticos, e estes transcritos para formulários específicos. Os dados foram analisados por estatística descritiva. Resultados: No total, foram avaliados 1.863 prontuários (92,6% adultos e 7,4% menores de 15 anos), com idade média 38 anos, sendo 818 indivíduos tratados com esquema paucibacilar, 886 multibacilar e 158 com outros esquemas terapêuticos, sendo que 585 (31,4%) haviam apresentado episódios de reação tipo 1 ou tipo 2. A média dos índices baciloscópicos (IB) dos cortes histológicos foi 1,62. No período avaliado, 158 indivíduos foram tratados tratados com outros esquemas. Do total de indivíduos avaliados, 151 apresentaram reativação da hanseníase, 27,1% tinham sido tratados com PQT/PB, 20,5% com PQT/MB e 52,3% com outros esquemas. Dos 24/41 indivíduos que fizeram esquema PB, somente 8 eram recidivas verdadeiras, 16 reativaram como MB e 17 fizeram tratamento irregular. Dentre os 31 indivíduos que fizeram esquema MB, 16 recidivaram e 8fizeram tratamento irregular. A porcentagem real de recidivas foi 1,28% no período avaliado. Conclusão: Os pacientes apresentaram baixa porcentagem de recidivas, isto se deve à alta eficácia da PQT, no entanto, esta não foi suficiente para o controle da endemia no município de Rondonópolis. A persistência bacilar pode ter papel relevante na recidiva, uma vez que se esperava o número maior de recidivas por reinfecção em uma área de alta endemia. Portanto, apesar do serviço de referência estar bem estruturado ele não é suficiente para cobrir a atual demanda de diagnósticos de hanseníase e exames de contatos para controle da endemia no município.

A estabilidade a longo prazo do tratamento ortodôntico é o objetivo dos ortodontistas na busca do sucesso dos casos clínicos. Desta forma o presente estudo objetivou avaliar retrospectivamente a influência da expansão rápida da maxila na estabilidade pós-contenção do alinhamento dos dentes ântero-superiores, em casos tratados com extração de pré-molares. A amostra foi constituída de 60 pacientes de ambos os gêneros, com más oclusões de Classe I e Classe II, tratados com extrações de 4 pré-molares, utilizando-se a mecânica de Edgewise. A amostra foi dividida em dois grupos, de acordo com o protocolo de tratamento, sendo o Grupo 1 composto por 30 pacientes (14 do gênero masculino e 1 do gênero feminino), com idade inicial média de 13,55 anos (d.p.= ± 1,58 anos), tratados ortodonticamente com extrações de quatro pré-molares. O Grupo 2 apresentou 30 pacientes (9 do gênero masculino e 21 do gênero feminino), com idade inicial média de 13,98 anos (d.p.= ± 2,61 anos), tratados ortodonticamente com expansão rápida da maxila e posteriormente mecânica corretiva com extrações de quatro pré-molares ou dois pré-molares superiores. Foram avaliados os modelos de estudo referentes às fases inicial (T1), final (T2) e pós-contenção (T3) de cada paciente, medindo-se o de Little, as distâncias intercaninos, interpré-molares, intermolares, o comprimento e o perímetro do arco. A análise estatística dos dados foi realizada pela análise de variância (ANOVA) a um critério para avaliação intragrupos entre as três fases. O teste de Tukey foi aplicado nas variáveis que apresentaram resultados estatisticamente significantes. A comparação intergrupos foi realizada pelo teste t independente. O teste de Pearson foi utilizado para correlacionar o Índice de Irregularidade de Little às demais variáveis estudadas. Os resultados evidenciaram que o Índice de Irregularidade de Little apresentou 9,40% de recidiva para o grupo 1 e 13,57% para o grupo 2. Não ocorreu diferença estatisticamente significante entre os grupos na recidiva das distâncias intercaninos, interpré-molares e intermolares, no comprimento e no perímetro do arco. Entretanto, o grupo 2 apresentou maior quantidade de recidiva na quantidade de apinhamento ântero-superior em relação ao grupo 1. Portanto, houve influência da expansão rápida da maxila na estabilidade do alinhamento dos incisivos superiores. / The long-term stability of orthodontic treatment is the objective of orthodontists in the search for success in clinical cases. Thus, the present retrospective study evaluated the influence of rapid maxillary expansion on the post-retention stability of alignment of maxillary anterior teeth in patients treated with premolar extraction. The sample was composed of 60 patients of both genders, with Class I and Class II malocclusions, treated by extraction of 4 premolars and edgewise mechanics. The sample was divided into two groups according to the treatment protocol. Group 1 comprised 30 patients (14 males and 16 females), with initial mean age 13.55 years (s.d. = ± 1.58 years), orthodontically treated by extraction of four premolars. Group 2 included 30 patients (9 males and 21 females), with initial mean age 13.98 years (s.d. = ± 2.61 years), orthodontically treated by rapid maxillary expansion followed by corrective mechanics with extraction of four premolars or two maxillary premolars. Dental casts obtained from all patients at initial (T1), final (T2) and postretention stages (T3) were assessed by measurements of the Little irregularity index, intercanine, interpremolar and intermolar distances, and length and perimeter of the maxillary arch. Statistical analysis of data was performed by one-way analysis of variance (ANOVA) for evaluation within groups among the three stages. The Tukey test was applied for the variables presenting statistically significant outcomes. Comparison between groups was performed by the independent t test. The Pearson test was used to correlate the Little irregularity index to the other study variables. The results demonstrated that the Little irregularity index presented 9.40% of relapse for Group 1 and 13.57% for Group 2. There was no statistically significant difference between groups as to the relapse in intercanine, interpremolar or intermolar distance, length and perimeter of the maxillary arch. However, Group 2 exhibited greater relapse in the amount of maxillary anterior crowding compared to Group 1. Thus, rapid maxillary expansion influenced the stability of alignment of maxillary incisors.

Prostate cancer is a leading cause of cancer-related death in men, and while many men diagnosed with the disease will have an indolent clinical course, 20-25% of men will experience disease recurrence which is invariably lethal. There is an urgent need for prognostic biomarkers that will predict disease recurrence and risk-stratify patients upon diagnosis, allowing for personalised therapies. This thesis attempts to identify new prognostic biomarkers for prostate cancer and investigates their patterns of protein expression in human primary prostate tumour tissue. Cancer stem cells are cancer cells thought to be uniquely capable of self-renewal and tumorigenicity, and may have a role in tumour recurrence. Using a literature searching approach, potential biomarkers related to stem cells, cancer stem cells or recurrence in prostate cancer were identified, and ALDH7A1, BMI1, SDC1, MUC1-C, Nestin and ZSCAN4 were chosen for investigation. An in silico approach was also used for biomarker identification, with RS1 and SLC31A1 selected as their mRNA was found to be upregulated in recurrent tumours. The expression patterns of all 7 potential biomarkers were examined by immunohistochemistry on prostate tumour tissue and benign tissue from prostate biopsies and prostatectomies. BMI1, ALDH7A1, MUC1-C and Nestin showed no relationship to recurrence or other clinical features. RS1 protein levels increased in patients with recurrence within 5 years, negatively correlated with AR expression, and a meta-analysis showed that the RS1 gene was amplified in up to 32% of castration-resistant prostate tumours. ZSCAN4 was heterogeneously expressed in a subset of 26% of prostate tumours with unclear characteristics and was not expressed in benign tissue, but was not associated with recurrence. Finally, SDC1 expression was lost in tumour epithelium, but a population of unidentified SDC1-expressing cells were found in the stroma of a third of tumours, and an increased burden of these cells was associated with primary Gleason pattern 5 tumours. These cells do not overlap with common epithelial, mesenchymal or stromal lineages, but may be migratory. In summary, the data presented in this thesis identifies 3 potential new biomarkers for prostate cancer, and provides the basis for future characterisation of their wider roles in the disease.

O presente estudo retrospectivo objetivou correlacionar a recidiva da sobremordida e da sobressaliência com a recidiva do apinhamento dos incisivos ântero-superiores e ântero-inferiores. A amostra consistiu de 34 pacientes (17 de cada gênero),apresentando más oclusões iniciais de Classe I e II,tratados sem extração e mecânica Edgewise.O tempo médio de duração do tratamento foi de 2,19 anos e os tempos de contenção e pós-contenção foram de 1,46 e 5,31 anos respectivamente. Todos os pacientes apresentavam, pelo menos, 3 mm de sobremordida e 4 mm de sobressaliência e apinhamento superior e inferior, de suave a severo. Foram medidos nos modelos de estudo das fases pré (T1), pós-tratamento (T2) e pós-contenção (T3) a sobremordida, a sobressaliência e o índice de irregularidade de Little superior e inferior. Após a obtenção dos dados, passou-se à análise estatística. A comparação intergrupos foi realizada por meio do teste t independente. Os testes ANOVA e Tukey foram apl icados para verificar se houve recidiva da sobremordida, da sobressaliência e dos apinhamentos ântero-superior e ântero-inferior. Para verificação da presença de correlação entre a recidiva da sobremordida, da sobressaliência e do apinhamento anterior, utilizou-se o teste de correlação de Pearson. Os resultados evidenciaram recidiva estat ist icamente signi ficante para o apinhamento ântero-super ior e ântero- infer ior . Houve correlação entre a recidiva da sobremordida e da sobressaliência, no entanto, não houve relação entre essas duas recidivas e o apinhamento anterior. / The present study aimed to correlate, by means of a retrospective analysis, the postretention stability of the overbite and overjet with the relapse of the crowding of maxillary and mandibular anterior teeth. The sample comprised 34 subjects (17 of each gender), at a mean initial age of 12.89 years, presenting Class I and II malocclusions, treated nonextraction and Edgewise mechanics.All patients presented at least 3mm of overbite and 4mm of overjet and maxillary and mandibular crowding from slight to severe. It was measured, in the dental casts from the stages pretreatment (T1), posttreatment (T2) and postretention (T3), the overbite, overjet and the maxillary and mandibular Little irregularity index. After data were obtained, the statistical analysis was performed. The intergroup comparison was performed by independent t tests. The ANOVA and Tukey tests were applied to verify the relapse of the overbite, overjet and maxillary and mandibular anterior crowding. To verify the presence of correlation among the relapse of the overbite, overjet and the anterior crowding, the Pearsons correlation test was used. Results did not show statistically significant difference between Angles Class I and Class II patients. There was correlation of the relapse of overbite with the relapse of overjet, however, there was no relationship among the relapse of overbite and overjet with the relapse of anterior crowding.

O crack, subproduto da cocaína, introduzida na década de 80 no Brasil, é um potente estimulador do Sistema Nervoso Central (SNC), desde a sua introdução no país, verificou-se que os efeitos no convívio social e familiar do usuário são quase imediatos, levando a sociedade e o estado a terem uma preocupação maior com o seu uso e controle. Devido à magnitude dos efeitos da abstinência das substâncias psicoativas (no caso o crack), a recaída apareceu como um fator comum no cotidiano dos usuários, para analisar esse fato se propôs na década de 70 um modelo de tratamento denominado Prevenção de Recaída (PR), baseado no modelo compensatório (Terapia cognitivo-comportamental) em que não há julgamento ou atribuição de culpa ao indivíduo pelo uso da droga, mas o leva à reflexão sobre seus atos e a se responsabilizar pelas mudanças de comportamento. Assim o objetivo desse estudo foi identificar os determinantes intrapessoais e interpessoais do processo de recaída em usuários de crack, além de identificar o perfil sociodemográfico, o inicio do uso e padrão de uso de crack e outras drogas (lícitas e ilícitas). Trata-se de um estudo qualitativo de teor descritivo. A pesquisa ocorreu em um CAPS ad II em uma cidade do interior de Minas Gerais e a amostra foi de conveniência. Foram realizadas entrevistas semi- estruturas em duas etapas, com intervalo de três meses cada uma com os mesmos participantes, foi aplicada a análise de conteúdo no tratamento dos dados qualitativos. Os dados sociodemográficos concordaram com a literatura nacional; exceto no que tange a média de idade. O início do consumo de drogas ocorreu com o uso de drogas lícitas na adolescência e a relação dos usuários de crack com as demais SPA (lícitas e ilícitas) mostrou-se ambivalente, não sendo reconhecidas como \"drogas\", particularmente o álcool, percebido também como gatilho ou porta de entrada para o uso do crack, já as recaídas apareceram atreladas a fatores intrapessoais e interpessoais, sendo que eles se retroalimentam, criando um círculo vicioso. O estudo mostrou que, no atendimento ao usuário de crack deve-se trabalhar com todas as facetas do uso ou do motivo da recaída, e identificar juntamente com o usuário, os gatilhos de recaída e a rede de apoio de que dispõe, fortalecendo-o na busca de mecanismos de autocontrole do uso / The crack, a byproduct of cocaine, introduced in the 80s in Brazil, is a potent stimulator of the central nervous system (CNS), since its introduction in the country, it was found that the effects on social and family life of the user are almost immediate , leading the society and the state to have a major concern with its use and control. Due to the magnitude of the effects of abstinence l of psychoactive substances (in this case crack), relapse appeared as a common factor in the daily lives of users, to analyze this fact was proposed in the 70\'s a model of treatment called Relapse Prevention (RP) based on the compensatory model (cognitive behavioral therapy) in which there is no judgment or blaming the individual for drug use, but leads to reflection on their actions and take responsibility for behavior change. Therefore the aim of this study was to identify intrapersonal and interpersonal determinants of relapse process in crack users, and identify the sociodemographic profile, the start of use and crack cocaine use pattern and other drugs (licit and illicit). This is a qualitative study of descriptive content. The research took place in a CAPS II ad in a city in Minas Gerais and the sample was a convenience. Semi-structures interviews were conducted in two stages, with an interval of three months each with the same participants were given the content analysis in the treatment of qualitative data. Socio-demographic data agreed with the national literature; except with respect to mean age. The start of drug use occurred with the use of illicit drugs in adolescence and crack users compared with other SPA (legal and illegal) proved to be ambivalent, not being recognized as \"drugs\", particularly alcohol use has also noticed as a trigger or gateway to crack use, since relapses appeared linked to intrapersonal and interpersonal factors, and they feed back, creating a vicious circle. The study showed that, in the care of crack users must work with all aspects of the use or reason of relapse, and identify with the user, the relapse triggers and the support network available to it, strengthening it in the pursuit of self- control mechanisms usage

L’addiction aux drogues d’abus se caractérise par une prise compulsive de drogue et par des épisodes récurrents de rechute après abstinence. Ces épisodes de rechute, parfois mortels, sont généralement précédés par un désir intense et irrépressible pour la drogue, appelé aussi craving. Bien que le rôle causal du craving dans la rechute reste encore à démontrer, la prévention du craving est devenue récemment un enjeu important des recherches clinique et préclinique. Chez l’homme l’amorçage du craving s’effectue après exposition ou réexposition à la drogue elle-même, à un stress, ou à des stimuli conditionnés à la prise de drogue. Chez l’animal, cet amorçage peut être modélisé par la reprise du comportement de recherche de drogue après arrêt du renforcement. Cette reprise peut être amorcée par les mêmes facteurs amorçant le craving chez l’homme, notamment par la réexposition à la drogue elle-même, ce qui suggère qu’elle exprime un état ressemblant au craving. Selon une hypothèse récente, l’amorçage du craving par la drogue serait dû à un conditionnement intéroceptif. Ce conditionnement se formerait au cours de l’acquisition où les animaux apprendraient à associer les stimuli intéroceptifs périphériques de la drogue avec la disponibilité du renforcement. Après arrêt du renforcement, la réexposition à ces stimuli intéroceptifs conditionnés provoquerait la reprise de la recherche de drogue en signalant (faussement) aux animaux le retour du renforcement. Cette hypothèse a permis le développement et la validation récente d’une stratégie anti-craving basée sur l’extinction de ces stimuli conditionnés de la cocaïne. Dans ce contexte, mon travail de thèse a eu pour but principal d’évaluer l’efficacité potentielle de cette stratégie à prévenir la rechute proprement dite, c’est-à-dire le retour aux niveaux de prise de cocaïne avant l’extinction. Ce travail a permis de démontrer : 1) qu’il est possible d’éteindre complètement l’amorçage du craving par la cocaïne chez l’animal ; 2) que cette extinction est accompagnée par une perte des réponses neuronales à la cocaïne dans les régions du cerveau causalement impliquées dans l’amorçage du craving (i.e., cortex préfrontal prélimbique et partie « core » du noyau accumbens); 3) mais que malgré nos attentes initiales, l’extinction complète et prolongée de l’amorçage du craving par la cocaïne n’a aucun effet préventif majeur sur la rechute, suggérant une dissociation entre craving et rechute, du moins chez l’animal ; enfin, 4) que cet échec relatif est dû en grande partie à l’existence d’une forme résiduelle de recherche de cocaïne résistante à l’extinction, fréquemment rapportée dans la littérature mais généralement ignorée. Cibler cette résistance à l’extinction afin de l’éradiquer devrait représenter un enjeu majeur pour la recherche future dans le domaine. / Craving often precedes relapse into cocaine addiction. This explains why considerable research effort is being expended to try to develop anti-craving strategies for relapse prevention. Recently, we discovered using the classic reinstatement model of cocaine craving that the reinstating or priming effect of cocaine can be extinguished with repeated priming – a phenomenon dubbed extinction of cocaine priming. Such extinction has been interpreted as evidence that the priming effect of cocaine on reinstatement of cocaine seeking depends on an interoceptive drug conditioning mechanism whereby the interoceptive cues of cocaine become reliable conditioned Pavlovian predictors of the availability of cocaine reinforcement. Regardless of the underlying mechanisms, however, extinction of drug priming has been proposed as a potential cocaine exposure therapy for relapse prevention that may complement other, more traditional exteroceptive cue exposure therapies. The goal of my PhD thesis was to measure the potential beneficial effect of this novel extinction strategy on subsequent relapse (i.e., return to the pre-extinction pattern of cocaine self-administration once the drug is made again available after extinction). Overall and contrary to our initial hope, extensive and complete extinction of cocaine priming had no major impact on relapse. This lack of effect occurred despite evidence for post-extinction loss of neuronal responsiveness to cocaine priming in brain regions causally involved in cocaine-induced reinstatement (i.e., the anterior cingulate and prelimbic prefrontal cortex, and the core of the nucleus accumbens). An effect of extinction of cocaine priming on relapse was only observed when cocaine was available for self-administration under more demanding conditions. However, this effect was modest and short-lived. Finally, we were able to trace the origin of our failure to prevent relapse to an extinction-resistant form of cocaine seeking that is commonly reported, though often overlooked, in other reinstatement studies. We propose that this behavior should become a novel target for future preclinical research on anti-craving strategies for relapse prevention.

This research project is intended to assist with the identification of relapse factors for alcoholics who have relapsed after their twelve‑step program. It is beneficial to understand relapse factors for alcoholics in order to provide effective treatment plans, services, and goals that will assist in attaining sobriety from alcohol. The research study used a qualitative approach; the data was collected through interviews from participants at the Cedar House agency in Bloomington, CA. The data was collected and then analyzed for possible themes of relapse factors. Themes that developed from interviews conducted with alcoholics that had relapsed after their twelve‑step programs were: commitment to therapy, unemployment, availability of healthy support, shame and guilt in seeking support, loneliness, and lack of support from family/peers and community. There are limitations to this study which, include a small sample size and interviews were held at only one agency that incorporated the twelve‑step process. Future studies should be implemented to confirm the results of this study.

The abuse of and addiction to drugs of abuse, such as tobacco, alcohol, opioids, and illicit drugs, are growing global problems that affect the welfare of individuals and societies worldwide. The National Institute of Drug Abuse estimates the annual cost of substance abuse to be over $740 billion in costs related to drug intoxication, withdrawal and relapse. A primary challenge in the treatment of substance abuse is the tendency of users to relapse following acute or extended periods of abstinence; on average over 60% of substance abusers will return to drug use within a year of receiving treatment, many relapsing following stressful life events. Central to the successful treatment of drug addiction is understanding the cellular mechanisms by which relapse episodes occur. Current data suggest that the activation of pituitary adenylate cyclase activating peptide (PACAP) systems in the bed nucleus of the stria terminalis (BNST) is an important event underlying stress-induced reinstatement to drug-seeking in a rodent model of stress-induced relapse. In conjunction with immunohistochemistry and pharmacological treatments, we used this behavioral model of stress-induced relapse to evaluate PACAP and PACAP type-1 receptor (PAC1-R) signaling in stress-induced reinstatement to cocaine seeking. Activation of the PAC1 receptor appears to be critical to stress-induced reinstatement, as the selective PAC1-R agonist, maxadilan, produced reinstatement behaviors in the absence of stress. Moreover, BNST pretreatment with either mitogen activated protein kinase-ERK (MEK) or endocytosis inhibitors to block extracellular signal-related kinase (ERK) signaling attenuated stress-induced reinstatement. Furthermore, BNST phosphorylated ERK (pERK) expression, mediated by PAC1-R activation, is substantially potentiated in cocaine-experienced animals after stressor exposure, in a manner that is dependent on endosomal signaling and MEK activity. These data suggest that the activation of a PAC1 signaling cascade is a key event underlying stress-induced reinstatement. Furthermore, this data may suggest a permanent change in the BNST PACAP system (sensitization) following cocaine exposure.

Resurgence refers to the reappearance of an extinguished operant behavior when reinforcement for an alternative behavior is also discontinued. It is especially relevant to the reappearance of problem behavior because many behavioral interventions discontinue reinforcement for aberrant behavior while simultaneously reinforcing an appropriate response. Existing information about the neuropharmacology of resurgence is scarce, but suggests overlap between drug seeking observed in the resurgence model and drug seeking observed in the more widely studied reinstatement and renewal models. The aim of this dissertation was to explore additional neural systems relevant to reinstatement and renewal preparations within a resurgence paradigm to assess further overlap. The neuropharmacology of resurgence was examined in two studies via administration of two drugs that have proven effective in blocking drug seeking in reinstatement and renewal preparations. In two experiments, rats earned food pellets for pressing a target lever in Phase I. In Phase II, lever pressing no longer produced food, but food was delivered contingent on an alterative nose poke response. Finally in Phase III, neither response produced food deliveries. Prior to these Phase III sessions, separate groups of rats were injected with 0, 50, or 100 mcg/kg of the dopamine D-2 receptor antagonist raclopride in Experiment 1 or 0, 20, or 40 mcg/kg of alpha-2 agonist clonidine in Experiment 2. Both doses of raclopride were effective in blocking resurgence, but there was strong evidence that the higher dose did so via motor rather than motivational impairment. Furthermore, the lower dose significantly suppressed the alternative nose poke, which suggests motor impairment, as well. Only the higher dose of clonidine blocked resurgence, but did so with no evidence of motor impairment. Raclopride significantly impacted extinction of the alternative poke at both doses tested, whereas clonidine had no effect at either dose. The results of the present studies provide additional information about the neuropharmacology of resurgence, as well as additional evidence of overlap between resurgence, reinstatement, and renewal. The present results may also have implications regarding underlying neural mechanisms and for pharmacotherapies to attenuate relapse when alternative sources of reinforcement are thinned or discontinued.