Treningsterapi som en del av tverrfaglig spesialisert rusbehandling. Formålet med studiet er å undersøke hvordan en gruppe pasienter med rusmiddelavhengighet og psykiske lidelser opplever og beskriver sine erfaringer med treningsterapi som en del av behandlingen ved Stiftelsen Bergensklinikkene. Dette sett i lys av Self-Determination Theory (SDT) - selvbestemmelsesteorien.    Studiet har en kvalitativ tilnærming hvor det empiriske materialet er basert på forskningsintervju. Det er blitt gjennomført intervjuer av syv pasienter med rusmiddelavhengighet alle med erfaring med bruk av treningsterapi ved Bergensklinikkene. Treningsterapi vil si planlagte og strukturerte fysiske aktiviteter. Empirien i dette studiet er analysert ved bruk av tradisjonell kvalitativ tilnærming og meningskonsentrering. Hovedfunnene viser at et autonomistøttende miljø er en forutsetning for å bli motivert for behandling. Brukermedvirkning og selvbestemmelse er faktorer som styrker motivasjonen for endring.   Økt kompetanse blant pasientene gjennom nye erfaringer og økt innsikt i treningsterapi, ga grunnlag for en autonomistyrt behandling.  Relasjon til treningsterapeutene var viktig for at pasientene opplevde terapeutens informasjon og veiledning som nyttig. Opplevelsen av et inkluderende felleskap med behandlere og medpasienter var av stor betydning for informantene. I studien kom det frem at behovet for tettere oppfølging i overgangen fra institusjon til hjem var nødvendig.     Opplevelse av bedre rusmestring, bedre søvn, mindre angst og depresjon og mindre ADHD-symptomer var viktige motivasjonsfaktorer. Dessuten ga fysiske effekter både indre og ytre motivasjon til bruk av treningsterapi. Gjennom studien kan en ut fra resultatene konkludere med at informantene blant annet vektlegger en autonomistøttende struktur, økt kompetanse, opplevelse av fellesskap og motivasjon som viktig og nødvendig i treningsterapi. / Excercise as therapy  Exercise as therapy as part of multidisciplinary specialized treatment. The purpose of the study is to understand how a group of patients with substance use disorders and mental illness experience and describe their experiences with exercise therapy as part of treatment at the Bergen Clinics Foundation. The thesis uses a framework of self-determination theory (SDT).   The study has a qualitative approach where the empirical material is based on research interviews. Seven patients were strategically selected to undertake semi-structured interviews regarding their experience with exercise as therapy as part of multidisciplinary specialized treatment in The Bergen Clinics Foundation. Exercise as therapy is physical activity that is planned and structured. The empirical data in this study is analyzed using the traditional qualitative approach.    The results show that an autonomy supportive environment is a prerequisite for being motivated for treatment. User involvement and self-determination are factors that strengthen the motivation for change.   Increased competence among patients through new experiences and greater insight into exercise as therapy, provided the basis for an autonomy-guided therapy. The patients´ relationship with the therapists was important: in case this relationship was deficient, they wouldn´t experience the information and guidance as helpful.   The experience of an inclusive community of practitioners and fellow patients was of great significance for patients. The study revealed that the need for closer monitoring of the transition from institutional to home was necessary.    Experience of better control of drug dependence, better sleep, less anxiety and depression and less ADHD symptoms were important motivators. Besides giving physical effects both intrinsic and extrinsic motivation for use of exercise as therapy.   One can conclude from the study that in the patients´ view an autonomy supportive structure, increased expertise, experience of community and motivation represented the most important and indispensable factors in exercise therapy.

La schizophrénie est une maladie mentale grave qui présente une comorbidité fréquente avec la toxicomanie et avec divers troubles immunitaires. Une méta-analyse réalisée récemment dans notre laboratoire a montré une augmentation d’IL-6 (une cytokine pro-inflammatoire), du récepteur soluble d’IL-2 (un marqueur d’activation du système immunitaire), et d’IL-1RA (une cytokine anti-inflammatoire) dans la schizophrénie, suggérant l’existence d’un syndrome inflammatoire dans cette maladie. La toxicomanie aussi est associée au dérèglement du réseau des cytokines inflammatoires, mais les effets dépendent du type de drogues et ils sont parfois diamétralement opposés. On dispose encore de peu d’informations sur le statut immunitaire et inflammatoire des patients qui ont un double diagnostic de schizophrénie et de toxicomanie. Le but de ce travail était d’explorer l’existence d’un état inflammatoire systémique chez les patients schizophrènes et toxicomanes, et l’influence du traitement avec un médicament antipsychotique atypique, la quétiapine. Les objectifs spécifiques étaient : 1) Mesurer les concentrations plasmatiques des cytokines inflammatoires chez les schizophrènes et toxicomanes avant, pendant et après traitement avec la quétiapine ; et 2) Faire des études de corrélations entre les taux de cytokines, les symptômes cliniques, et la consommation de drogues. Les résultats montrent que comparativement aux contrôles normaux, les patients avec un double diagnostic présentent une augmentation d’IL-6, d’IL-1RA, du sIL-2R et d’IL-8 avant traitement à la quétiapine. Les augmentations des concentrations plasmatiques d’IL-1RA sont particulièrement importantes chez les patients avec double diagnostic, si on les compare à celles publiées chez les schizophrènes sans toxicomanie. Le traitement à la quétiapine n’influence pas les concentrations plasmatiques de ces cytokines, sauf sIL-2R qui augmente davantage au cours du traitement. Des corrélations positives de puissance modérée sont retrouvées entre IL-6 et dépression, IL-6 et alcool, IL-1RA et cognition, IL-8 et dépression, IL-8 et alcool, sIL-2R et cannabis. Notre étude révèle que la réponse inflammatoire est activée chez les schizophrènes et toxicomanes. De plus, la toxicomanie semble jouer un rôle facilitant ou potentialisateur dans les augmentations des taux circulants d’IL-1RA. Les études en cours sur différentes populations de schizophrènes avec ou sans toxicomanie, et chez des toxicomanes non schizophrènes permettront de préciser le rôle des différentes drogues d’abus dans le syndrome inflammatoire chez les schizophrènes, ainsi que les implications de ce syndrome sur le plan clinique et thérapeutique. / Schizophrenia is a psychosis which presents a frequent comorbidity with substance use disorders (SUD) and with various immune alterations. Using meta-analysis, we have demonstrated previously establishment of an inflammatory syndrome in schizophrenia patients, illustrated by elevated circulating levels of IL-6 (a pro-inflammatory cytokine), sIL-2R (marker of immune activation) and IL-1RA (an anti-inflammatory cytokine). SUD is also associated with dysregulation of inflammatory cytokines, but the effects may depend on the type of substance of abuse. The goal of this project was: 1) To measure plasma concentrations of inflammatory cytokines in schizophrenia patients with comorbid SUD, before, during and after treatment with an atypical antipsychotic, quetiapine; and 2) To perform correlation studies between plasma concentrations of inflammatory cytokines and clinical symptoms, including positive and negative symptoms, cognition, depression and substance use. Relative to normal controls, patients with a dual diagnosis showed increased plasma concentrations of IL-6, IL-1RA, sIL-2R, and IL-8 at baseline, IL-1RA increases being the most important. Quetiapine treatment did not influence plasma cytokine concentrations, except sIL-2R which increased further. Moderate positive correlations were found between IL-6 and depression, IL-6 and alcohol, IL-1RA and cognition, IL-8 and depression, IL-8 and alcohol and between sIL-2R and cannabis. This study demonstrates that the immune and inflammatory response is activated in schizophrenia patients with comorbid SUD. Furthermore, SUD may play a facilitating or potentiating role in the increases in peripheral levels of IL-1RA. Ongoing studies in different patient populations with schizophrenia with or without SUD, and patients with SUD alone will help elucidate the role of different substances of abuse in the inflammatory syndrome in schizophrenia, as well as the clinical and therapeutic relevance of this syndrome.

The focus of the thesis is on drug addiction prevention in families. Education in the family is seen here as one of the key factors preventing substance addiction. In my work, I emphasize the need to inform and educate parents in this area and put forward solutions in the form of the project "Educating Parents in Children's Drug Addiction Problems". The purpose of the project is to publish a handbook for parents titled "Do You Know About Drugs What Your Child Does?" The publication will provide parents with basic information about drug addiction. In addition to theoretical knowledge about drugs, parents will also be offered practical advice and guidance on how to prevent potential problems with drugs in their children, on how to react when they learn about the child's experimentation with drugs and, last, but not least, how to act in the situation when they find out that their child is already drug-addicted. Prior to writing the handbook, quantitative survey of parents has been undertaken to map the situation in the area of drug addiction prevention in families. The aim is to include the results of the survey in the handbook in such a way that, e.g., its text, in some parts, will give details to the explanation of the problematic phenomena exposed by the survey. The survey is one part of an entire...

As comunidades terapêuticas para dependentes químicos são importantes recursos, descritos pela Secretária Nacional Antidrogas, na rede de atenção aos transtornos relacionados ao abuso de substâncias psicoativas. A equipe profissional nestas comunidades terapêuticas é representada, principalmente, por conselheiros em dependência química. É consenso entre os especialistas, pela complexidade desta problemática, que o tratamento deve abordar o paciente em seu contexto sociofamiliar (Stanton e Todd, 1990). O presente estudo tem como objetivo apresentar e avaliar um programa de tratamento e prevenção para dependentes químicos em comunidades terapêuticas com foco em seu contexto sociofamiliar, por nós denominado TRA: terapia de rede para adictos. Um programa destinado aos conselheiros em dependência química, que trabalham nestas comunidades. Fundamentados no pensamento-novo-paradigmático, de Esteves de Vasconcellos (2002), e na representação social, de Moscovici (2003), utilizamos como método uma pesquisa interventiva, com delineamento qualitativo construtivista, baseado em Pakman (1995), o que significa, no contexto deste trabalho, que o modelo de TRA foi construído em conjunto com os participantes: conselheiros e pacientes da comunidade terapêutica na qual realizamos a pesquisa. As principais técnicas empregadas foram: a família de origem do conselheiro e o discurso do sujeito coletivo (DSC), de acordo com Lefèvre e Lefèvre (2003). Para a análise dos resultados, usamos a técnica de triangulação de dados, segundo Denzin e Lincoln (2000). Os resultados obtidos contribuíram para conhecermos as representações sociais dos participantes sobre suas famílias e, sistemicamente, compreendermos os múltiplos aspectos envolvidos na complexidade do ciclo da drogadicção. As téc nicas interventivas auxiliaram no resgate dos aspectos resilientes e das competências dos sistemas familiares e no empoderamento da comunidade terapêutica, dos pacientes e de suas famílias, para lidar com os problemas da dependência química. Estas técnicas também colaboraram para a compreensão e a abordagem da imprevisibilidade ocorrida, em vários âmbitos, no desenvolvimento da pesquisa. As diferentes representações sociais nos DSC foram analisadas sob o olhar da intersubjetividade, proporcionando uma rica troca entre os participantes. A coparticipação, na elaboração deste modelo, contribuiu, principalmente, para a coconstrução de um novo saber em prevenção e tratamento para as comunidades terapêuticas, com um olhar mais amplo e globalizador, para o sistema familiar e outros sistemas envolvidos no problema da drogadicção / Therapeutic communities for chemical dependents are important resources, described by National Antidrug Secretary, to the network of care for disorders related to the abuse of psychoactive substances. The professional team in these therapeutic communities and represented, mainly, by advisers in chemical dependency. There is a consensus among the experts, the complexity of the problem, that treatment must approach the patient in their family environment (Stanton and Todd, 1990). The purpose of the present study is to present and assess a program of prevention and treatment for chemical dependents in therapeutic communities with a focus on their family environment, we called TRA: therapy of network for addiction. A program for counselor in chemical dependency, working in these communities. Based on thought-new-paradigmatic, Esteves de Vasconcellos (2002), and the social representation of Moscovici (2003), we used the method an interventional research, with qualitative design constructivist, based in Pakman (1995), which means, in the context of this work, that the model of TRA was built together with the participants, counselors, and patients in the therapeutic community where we have the research. The main techniques used were: the family of origin of the counselor and the collective subject discourse (DSC), according to Lefèvre and Lefèvre (2003). For the analysis of the results, we used the technique of data triangulation, second Denzin and Lincoln (2000). The results contributed to know the social representations of the participants on their families, and systemically, we understand the many aspects involved in the complexity of the cycle of drug-addiction. The interventional techniques helped with the rescue of the aspects resilient and the skills of the family systems and the empowerment of the therapeutic community, patients and their families to approach with the problems of chemical dependency. These techniques also collaborated for the understanding and approach of unpredictability that occurred in a number of areas in the development of the research. The different social representations in DSC were analyzed under the gaze of the intersubjectivity, providing a rich Exchange of views between the participants. The participation in colaboration, in drawing up this model contributed mainly to build together a new knowledge in treatment and prevention for the therapeutic communities, with a broader perspective and global vision, for the family system and other systems involved in the problem of drug-addiction

As comunidades terapêuticas para dependentes químicos são importantes recursos, descritos pela Secretária Nacional Antidrogas, na rede de atenção aos transtornos relacionados ao abuso de substâncias psicoativas. A equipe profissional nestas comunidades terapêuticas é representada, principalmente, por conselheiros em dependência química. É consenso entre os especialistas, pela complexidade desta problemática, que o tratamento deve abordar o paciente em seu contexto sociofamiliar (Stanton e Todd, 1990). O presente estudo tem como objetivo apresentar e avaliar um programa de tratamento e prevenção para dependentes químicos em comunidades terapêuticas com foco em seu contexto sociofamiliar, por nós denominado TRA: terapia de rede para adictos. Um programa destinado aos conselheiros em dependência química, que trabalham nestas comunidades. Fundamentados no pensamento-novo-paradigmático, de Esteves de Vasconcellos (2002), e na representação social, de Moscovici (2003), utilizamos como método uma pesquisa interventiva, com delineamento qualitativo construtivista, baseado em Pakman (1995), o que significa, no contexto deste trabalho, que o modelo de TRA foi construído em conjunto com os participantes: conselheiros e pacientes da comunidade terapêutica na qual realizamos a pesquisa. As principais técnicas empregadas foram: a família de origem do conselheiro e o discurso do sujeito coletivo (DSC), de acordo com Lefèvre e Lefèvre (2003). Para a análise dos resultados, usamos a técnica de triangulação de dados, segundo Denzin e Lincoln (2000). Os resultados obtidos contribuíram para conhecermos as representações sociais dos participantes sobre suas famílias e, sistemicamente, compreendermos os múltiplos aspectos envolvidos na complexidade do ciclo da drogadicção. As téc nicas interventivas auxiliaram no resgate dos aspectos resilientes e das competências dos sistemas familiares e no empoderamento da comunidade terapêutica, dos pacientes e de suas famílias, para lidar com os problemas da dependência química. Estas técnicas também colaboraram para a compreensão e a abordagem da imprevisibilidade ocorrida, em vários âmbitos, no desenvolvimento da pesquisa. As diferentes representações sociais nos DSC foram analisadas sob o olhar da intersubjetividade, proporcionando uma rica troca entre os participantes. A coparticipação, na elaboração deste modelo, contribuiu, principalmente, para a coconstrução de um novo saber em prevenção e tratamento para as comunidades terapêuticas, com um olhar mais amplo e globalizador, para o sistema familiar e outros sistemas envolvidos no problema da drogadicção / Therapeutic communities for chemical dependents are important resources, described by National Antidrug Secretary, to the network of care for disorders related to the abuse of psychoactive substances. The professional team in these therapeutic communities and represented, mainly, by advisers in chemical dependency. There is a consensus among the experts, the complexity of the problem, that treatment must approach the patient in their family environment (Stanton and Todd, 1990). The purpose of the present study is to present and assess a program of prevention and treatment for chemical dependents in therapeutic communities with a focus on their family environment, we called TRA: therapy of network for addiction. A program for counselor in chemical dependency, working in these communities. Based on thought-new-paradigmatic, Esteves de Vasconcellos (2002), and the social representation of Moscovici (2003), we used the method an interventional research, with qualitative design constructivist, based in Pakman (1995), which means, in the context of this work, that the model of TRA was built together with the participants, counselors, and patients in the therapeutic community where we have the research. The main techniques used were: the family of origin of the counselor and the collective subject discourse (DSC), according to Lefèvre and Lefèvre (2003). For the analysis of the results, we used the technique of data triangulation, second Denzin and Lincoln (2000). The results contributed to know the social representations of the participants on their families, and systemically, we understand the many aspects involved in the complexity of the cycle of drug-addiction. The interventional techniques helped with the rescue of the aspects resilient and the skills of the family systems and the empowerment of the therapeutic community, patients and their families to approach with the problems of chemical dependency. These techniques also collaborated for the understanding and approach of unpredictability that occurred in a number of areas in the development of the research. The different social representations in DSC were analyzed under the gaze of the intersubjectivity, providing a rich Exchange of views between the participants. The participation in colaboration, in drawing up this model contributed mainly to build together a new knowledge in treatment and prevention for the therapeutic communities, with a broader perspective and global vision, for the family system and other systems involved in the problem of drug-addiction

A fundamental question in the neurobiological study of drug addiction concerns the mechanisms mediating the motivational effects of chronic drug withdrawal. According to one theory, drugs of abuse activate opposing motivational processes after both acute and chronic drug use. The negative experience of withdrawal is the opponent process of chronic drug use that drives relapse to drug-seeking and -taking, making the identification of the neurobiological substrates mediating withdrawal an issue of central importance in addiction research. In this thesis, I identify the involvement of the neurotransmitters dopamine (DA) and corticotropin-releasing factor (CRF) in the opponent motivational a- and b-processes occurring after acute and chronic nicotine administration. I report that acute nicotine stimulates an initial aversive a-process followed by a rewarding opponent b-process, and chronic nicotine stimulates a rewarding a-process followed by an aversive opponent b-process (withdrawal). These responses can be modeled using a place conditioning paradigm. I demonstrate that the acute nicotine a-process is mediated by phasic dopaminergic activity and the DA receptor subtype-1 (D1R) but not by tonic dopaminergic activity and the DA receptor subtype-2 (D2R) or CRF activity, and the opponent b-process is neither DA- nor CRF-mediated. I also demonstrate that the chronic nicotine a-process is DA- but not CRF-mediated, and that withdrawal from chronic nicotine (the b-process) decreases tonic but not phasic DA activity in the ventral tegmental area (VTA), an effect that is D2R- but not D1R-mediated. I show that a specific pattern of signaling at D1Rs and D2Rs mediates the motivational responses to acute nicotine and chronic nicotine withdrawal, respectively, by demonstrating that both increasing or decreasing signaling at these receptors prevents the expression of the conditioned motivational response. Furthermore, I report that the induction of nicotine dependence increases CRF mRNA in VTA DA neurons, and that blocking either the upregulation of CRF mRNA or the activation of VTA CRF receptors prevents the anxiogenic and aversive motivational responses to withdrawal from chronic nicotine. The results described in this thesis provide novel evidence of a VTA DA/CRF system, and demonstrate that both CRF and a specific pattern of tonic DA activity in the VTA are necessary for the aversive motivational experience of nicotine withdrawal.

Narkotikų kontrolės ir narkomanijos prevencijos politiką įgyvendina narkotikų kontrolės departamentas, Vyriausybė tobulina teisinę bazę narkotikų prevencijos srityje, vykdomos visuomenės sveikatos priežiūros reformos kryptys, kuriomis siekiama daugiau dėmesio skirti sveikatos išsaugojimui, rizikos veiksnių poveikio sumažinimui. Prevencijos priemonės mokyklose glaudžiai siejasi su vaikų sveikos gyvensenos ugdymu – viena pagrindinių mokyklos sveikatos priežiūros specialistų veiklos krypčių. Per pastaruosius metus atlikta nemažai narkotikų paplitimo tarp mokinių tyrimų, vertinta ir prevencinės darbo grupės veikla. Nuo 2002 m. kasmet atliekamos mokyklose dirbančių slaugytojų veiklos studijos. Tačiau mokyklos sveikatos priežiūros specialisto veiklos tyrimas narkomanijos prevencijos aspektu dar nebuvo atliktas. Šio tyrimo tikslas: įvertinti mokyklos sveikatos priežiūros specialisto vykdomą veiklą narkomanijos prevencijoje. Tyrimas atliktas aštuoniose Lietuvos mokyklose apklausus 240 respondentų: 150 mokinių, 40 mokyklos darbo grupės narių ir 8 mokyklos sveikatos priežiūros specialistų, bei 42 mokyklos sveikatos priežiūros specialistai, dalyvavę Klaipėdos visuomenės sveikatos centro organizuotame seminare. Apklausai naudotos anoniminės anketos visoms trims respondentų grupėms, duomenys apdoroti panaudojant SPSS programinį paketą. Nustatyta, kad 11,3 proc. mokinių jau pabandė narkotinių medžiagų. Tyrimas atskleidė tokią tendenciją, kad 72,7 proc. mokinių nurodė, jog žino... [toliau žr. visą tekstą] / Policy of narcotic control and drug addiction prevention is realised by Drug control department, Government continuously improves juridical basis of drug addiction prevention, different reforms in public health care activities are implemented, by the help of which it is seeked to pay greater attention to health retention as well as reduction of risk factors impact. Prevention activities at schools are tightly connected with children education about healthy lifestyle upbringing and these are one of the main tasks for school health care specialists. During last years quite many research works in the field of spread of narcotics have been performed. Impact of prevention workgroup was analysed as well. Since 2002 every year different research studies of school nurses activities are carried out. Despite of wide range of such research studies activities of school health care specialist in the field of drug addiction prevention haven‘t been evaluated. The goal of the study was to evaluate role of school health care specialist in the field of drug addiction prevention. The study was performed in eight schools of Lithuania. 240 respondents were involved: 150 schoolchildren, 40 school workgroup members, 8 school health care specialists and 42 school health care specialists, who attended the seminar organised by Klaipėda public health centre. The questionnaires were anonymous for all three respondent groups. Statistical analysis was performed using SPSS statistical package. It was... [to full text]

La schizophrénie est une maladie mentale grave qui présente une comorbidité fréquente avec la toxicomanie et avec divers troubles immunitaires. Une méta-analyse réalisée récemment dans notre laboratoire a montré une augmentation d’IL-6 (une cytokine pro-inflammatoire), du récepteur soluble d’IL-2 (un marqueur d’activation du système immunitaire), et d’IL-1RA (une cytokine anti-inflammatoire) dans la schizophrénie, suggérant l’existence d’un syndrome inflammatoire dans cette maladie. La toxicomanie aussi est associée au dérèglement du réseau des cytokines inflammatoires, mais les effets dépendent du type de drogues et ils sont parfois diamétralement opposés. On dispose encore de peu d’informations sur le statut immunitaire et inflammatoire des patients qui ont un double diagnostic de schizophrénie et de toxicomanie. Le but de ce travail était d’explorer l’existence d’un état inflammatoire systémique chez les patients schizophrènes et toxicomanes, et l’influence du traitement avec un médicament antipsychotique atypique, la quétiapine. Les objectifs spécifiques étaient : 1) Mesurer les concentrations plasmatiques des cytokines inflammatoires chez les schizophrènes et toxicomanes avant, pendant et après traitement avec la quétiapine ; et 2) Faire des études de corrélations entre les taux de cytokines, les symptômes cliniques, et la consommation de drogues. Les résultats montrent que comparativement aux contrôles normaux, les patients avec un double diagnostic présentent une augmentation d’IL-6, d’IL-1RA, du sIL-2R et d’IL-8 avant traitement à la quétiapine. Les augmentations des concentrations plasmatiques d’IL-1RA sont particulièrement importantes chez les patients avec double diagnostic, si on les compare à celles publiées chez les schizophrènes sans toxicomanie. Le traitement à la quétiapine n’influence pas les concentrations plasmatiques de ces cytokines, sauf sIL-2R qui augmente davantage au cours du traitement. Des corrélations positives de puissance modérée sont retrouvées entre IL-6 et dépression, IL-6 et alcool, IL-1RA et cognition, IL-8 et dépression, IL-8 et alcool, sIL-2R et cannabis. Notre étude révèle que la réponse inflammatoire est activée chez les schizophrènes et toxicomanes. De plus, la toxicomanie semble jouer un rôle facilitant ou potentialisateur dans les augmentations des taux circulants d’IL-1RA. Les études en cours sur différentes populations de schizophrènes avec ou sans toxicomanie, et chez des toxicomanes non schizophrènes permettront de préciser le rôle des différentes drogues d’abus dans le syndrome inflammatoire chez les schizophrènes, ainsi que les implications de ce syndrome sur le plan clinique et thérapeutique. / Schizophrenia is a psychosis which presents a frequent comorbidity with substance use disorders (SUD) and with various immune alterations. Using meta-analysis, we have demonstrated previously establishment of an inflammatory syndrome in schizophrenia patients, illustrated by elevated circulating levels of IL-6 (a pro-inflammatory cytokine), sIL-2R (marker of immune activation) and IL-1RA (an anti-inflammatory cytokine). SUD is also associated with dysregulation of inflammatory cytokines, but the effects may depend on the type of substance of abuse. The goal of this project was: 1) To measure plasma concentrations of inflammatory cytokines in schizophrenia patients with comorbid SUD, before, during and after treatment with an atypical antipsychotic, quetiapine; and 2) To perform correlation studies between plasma concentrations of inflammatory cytokines and clinical symptoms, including positive and negative symptoms, cognition, depression and substance use. Relative to normal controls, patients with a dual diagnosis showed increased plasma concentrations of IL-6, IL-1RA, sIL-2R, and IL-8 at baseline, IL-1RA increases being the most important. Quetiapine treatment did not influence plasma cytokine concentrations, except sIL-2R which increased further. Moderate positive correlations were found between IL-6 and depression, IL-6 and alcohol, IL-1RA and cognition, IL-8 and depression, IL-8 and alcohol and between sIL-2R and cannabis. This study demonstrates that the immune and inflammatory response is activated in schizophrenia patients with comorbid SUD. Furthermore, SUD may play a facilitating or potentiating role in the increases in peripheral levels of IL-1RA. Ongoing studies in different patient populations with schizophrenia with or without SUD, and patients with SUD alone will help elucidate the role of different substances of abuse in the inflammatory syndrome in schizophrenia, as well as the clinical and therapeutic relevance of this syndrome.

Addiction to drugs is a widely acknowledged problem in South Africa. Newer developments in the study of addiction include behaviours such as gambling and sex as part of a broader syndrome. International research has established that most people with one addiction are at risk for co-occurring addictions which are frequently undiagnosed and untreated. Multiple addictions (MA) have been shown to combine in specific patterns to produce addiction interaction disorder (AID) resulting in a more complex, treatment- resistant illness. This was the first study South Africa to investigate if people with substance use disorders had other addictions. The research had three aims: to establish if in-patients admitted to three drug rehabilitation centres had other addictions, to investigate the extent of the MA and AID and to determine whether the treatment programmes managed them appropriately. The study employed the mixed methods research design and was located at three in-patient facilities in Durban, KwaZulu-Natal. During the first phase, discussion groups were held with professionals that explored their perceptions of MA, AID and current treatment programmes. The second phase involved a survey of 123 participants screened for poly-substance abuse, sex (including internet) addiction and problem gambling. The third phase utilised in-depth interviews with 25 participants displaying MA to understand the development of addiction, AID and treatment received. The data were analysed utilising descriptive and statistical analysis for the survey data, and thematic analysis for the in-depth interviews and discussion groups. The study found a high incidence of MA within the survey population of 54%; 37% of participants tested positive or at risk for problem gambling and 41% tested positive for sex addiction with 24% of the participants being positive for both. In-depth interviews revealed high rates of trauma, especially for the female participants and demonstrated the complex interrelationship between addictions. AID was identified in all 25 participants. In KwaZulu- Natal, it appears that MA and AID are currently not being assessed or treated. The study highlights the need for a broader conceptualisation of addiction which would improve current assessment and treatment and has implications for further training of professionals and addiction policy in South Africa. / Ph.D. University of KwaZulu-Natal, Durban 2013.

A fundamental question in the neurobiological study of drug addiction concerns the mechanisms mediating the motivational effects of chronic drug withdrawal. According to one theory, drugs of abuse activate opposing motivational processes after both acute and chronic drug use. The negative experience of withdrawal is the opponent process of chronic drug use that drives relapse to drug-seeking and -taking, making the identification of the neurobiological substrates mediating withdrawal an issue of central importance in addiction research. In this thesis, I identify the involvement of the neurotransmitters dopamine (DA) and corticotropin-releasing factor (CRF) in the opponent motivational a- and b-processes occurring after acute and chronic nicotine administration. I report that acute nicotine stimulates an initial aversive a-process followed by a rewarding opponent b-process, and chronic nicotine stimulates a rewarding a-process followed by an aversive opponent b-process (withdrawal). These responses can be modeled using a place conditioning paradigm. I demonstrate that the acute nicotine a-process is mediated by phasic dopaminergic activity and the DA receptor subtype-1 (D1R) but not by tonic dopaminergic activity and the DA receptor subtype-2 (D2R) or CRF activity, and the opponent b-process is neither DA- nor CRF-mediated. I also demonstrate that the chronic nicotine a-process is DA- but not CRF-mediated, and that withdrawal from chronic nicotine (the b-process) decreases tonic but not phasic DA activity in the ventral tegmental area (VTA), an effect that is D2R- but not D1R-mediated. I show that a specific pattern of signaling at D1Rs and D2Rs mediates the motivational responses to acute nicotine and chronic nicotine withdrawal, respectively, by demonstrating that both increasing or decreasing signaling at these receptors prevents the expression of the conditioned motivational response. Furthermore, I report that the induction of nicotine dependence increases CRF mRNA in VTA DA neurons, and that blocking either the upregulation of CRF mRNA or the activation of VTA CRF receptors prevents the anxiogenic and aversive motivational responses to withdrawal from chronic nicotine. The results described in this thesis provide novel evidence of a VTA DA/CRF system, and demonstrate that both CRF and a specific pattern of tonic DA activity in the VTA are necessary for the aversive motivational experience of nicotine withdrawal.