Thesis (PhD (Biomedical Sciences. Medical Physiology))--University of Stellenbosch, 2010. / ENGLISH ABSTRACT: Psychosocial stressors have frequently been associated with an increased risk for developing The contributions of the cholinergic (Lobeline) and opioid (Naltrexone) systems in place preference behaviour were determined by employing a post-methamphetamine pharmacological treatment strategy. These two treatments failed to reverse the methamphetamine-induced place preference. However, administration of the drugs did lead to alterations in striatal dopamine and serotonin levels which may infer beneficial effects against the biochemical alterations induced by methamphetamine. We used both 2-D gel-based proteomics and isobaric tagging for relative and absolute quantitation (iTRAQ) to identify proteins in the frontal cortex, and nucleus accumbens shell and core of rats that were subjected to maternal separation, methamphetamine or both regimes. The proteins were associated with cytoskeletal modifications, altered energy metabolism, degenerative processes, interruptions in normal neurotransmission and enhanced intracellular signalling. We found that more proteins were quantitatively expressed in rats that were exposed to maternal separation followed by methamphetamine treatment than those animals subjected to the individual interventions independently. Additional proteins recruited by the combination of MS followed by MA which remained unchanged with independent treatments included malate dehydrogenase, V-type proton ATPase subunit E1, beta-synuclein, brevican core protein, eukaryotic translation initiation factor 4H, histidine triad nucleotide binding protein 1 and stress-induced phosphoprotein in the nucleus accumbens shell subregion. Additional proteins recruited in the core subregion with the combination treatment included thymosin beta-4, calretinin, Arpp-21 protein, alpha-synuclein, ubiquitin carboxylterminal hydrolase isozyme L1, cytochrome c, brain acid soluble protein 1, prosaposin and stress-induced phosphoprotein 1. Although, on a behavioural level via the use of CPP we found that MS did not exacerbate the rewarding effects of MA, the proteomic data does infer a role played by early life stress by the recruitment of additional proteins. We therefore propose that the molecular mechanisms by which early adverse events predispose animals to the addictive state may involve a complex assembly of cellular processes within the brain. depression, anxiety or substance abuse in adult life. Animal studies have also suggested that stressful experiences may result in altered behavioural responses to drugs of abuse as evidenced by enhanced cocaine self-administration and psychostimulant-induced hyperlocomotor activity. The main aim of our study was to establish whether adversity early in life would render individuals more vulnerable to later drug usage. We adopted maternal separation as our animal model of early life adversity and treated these animals with methamphetamine during the adolescent stage of their life. A conditioned place preference (CPP) paradigm was subsequently used to determine the rewarding effects of methamphetamine. To obtain an understanding of the underlying molecular mechanisms of methamphetamine-induced behaviour, we measured neurochemical changes on a neuroendocrine, neurotrophic, neurotransmitter and proteome level. Firstly, we established that methamphetamine-induced place preference behaviour lasted for at least 2 weeks after the last methamphetamine administration. Contrary to expectation, this behaviour was not affected by prior exposure to maternal separation. However, rats subjected to maternal separation caused a decrease in apomorphine-induced locomotor behaviour in methamphetamine-treated rats. Maternal separation therefore preferentially affected the behavioural repertoire of the dorsal striatum rather than that of the ventral striatum. A general down regulation of neuroendocrine activity (ACTH and corticosterone levels) was observed in animals subjected to maternal separation or methamphetamine treatment, as well as those subjected to the combination of the two interventions. Increased concentrations of plasma prolactin levels in maternally separated as well as normally reared animals subjected to methamphetamine-CPP were found which suggested a reduction in dopamine inhibition. Maternal separation resulted in increased NGF levels in the ventral hippocampus of methamphetamine treated rats. This suggested that the ventral hippocampus may particularly be vulnerable to the effects of early life stress. The increased neurotrophin concentrations may reflect a compensatory response to stress and drug exposure. / AFRIKAANSE OPSOMMING: Psigososiale stressors word gereeld geassosieer met ‘n verhoogde risiko vir die ontwikkeling van depressie, angs en dwelm misbruik in volwassenheid. Diere studies het ook al bewys dat vroeë lewensstres in die vorm van moederlike skeiding lei tot veranderde gedrag teenoor dwelm misbruik. Hierdie veranderde gedrag veroorsaak deur moederlike skeiding sluit die verhoodge kokaïne toediening en psigostimulant geinduseerde verhoging in lokomotoriese aktiwiteit in. Die hoofdoel van die studie was om vas te stel of vroeë lewensstres mense meer vatbaar laat vir latere dwelm misbruik. ‘n Moederlike skeidings diere model was gebruik om vroeë lewensstres voor te stel and het verder hierdie diere behandel met metamfetamiene gedurende adolesensie. Die gekondisioneerde plek voorkeur model was gebruik om die euforiese / verslawende effekte van metamfetamiene te bepaal. Om die onderliggende molekulêre meganismes van metamfetamien geinduseerde gedrag te verstaan het ons neurochemiese veranderinge op ‘n neuroendokriene, neurotrofiese, neurotransmissie en proteinvlak vasgestel. Eerstens het ons was gestel dat metamfetamien geinduseerde plek voorkeur vir ten minste twee weke na die laaste metafetamien toediening voortduur. In teenoorstelling met verwagting, het moederlike skeiding nie metamfetamien geinduseerde plek voorkeur beinvloed nie, maar eerder apo-morfien geinduseerde lokomotoriese aktiwiteit geaffekteer. Moederlike skeiding stres het by voorkeur die gedrags funksie van die dorsale striatum beinvloed eerder as die ventrale gedragsfunksie. ‘n Algemene afregulering van neuroendokriene aktiwiteit was waargeneem (adrenokortikotrofiene en kortikosteroon vlakke) in diere wat aan moederlike skeiding of metafetamien behandeling sowel as die kombinasie behandeling blootgestel was. Verhoogde plasma prolaktien vlakke was gevind in moederlike skeidings rotte sowel as kontrole diere wat verder blootgestel is aan metamfetamien behandeling wat ‘n inhibisie van die dopamiene sisteem toon. Moederlike skeiding het ook ‘n verhooging in neurotrofiene (NGF) in die ventrale hippokampus van metamfetamien behandelde rotte veroorsaak. Hierdie bevinding stel voor dat die ventrale hippokampus veral vatbaar is vir die effekte van vroeë lewensstres. ‘n Verhoging in neurotrofien konsentrasies mag ‘n kompenserende teenslag van die brein wees teen stres en dwelm blootstelling. Die bydrae van die cholinergiese (Lobeline) en opiaat (Naltrexone) sisteme in plek voorkeur gedrag was bepaal deur farmaseutiese behandeling te volg na metamftemien toediening. Lobeline en naltrexone was egter nie suksesvol om die metamfetamien geinduseerde plek voorkeur te wysig nie. Alhoewel die toediening van die twee behandelings het tot veranderinge in neurotransmissie (dopamiene en serotoniene) gelei wat moontlik tot voordelige effekte teen die biochemiese veranderinge van metamfetamien kan lei. Om veranderinge op proteinvlak in die frontale korteks en nukleus akkumbens middel en buitenste subareas vas te stel het ons gebruik gemaak van twee-dimensie gel elektroforese en isobariese merkers vir relatiewe en absolute kwantifisering (iTRAQ) gevolg deur massa spektrofotometrie. Geindentifiseerde proteine was geassosieer met sitoskeletale modifikasies, veranderde energie metabolisme, afbrekende prosesse, onderbrekings met normale neurotransmissie en intrasellulêre seintransduksie. Meer proteine was beduidend in die diere wat aan beide moederlike skeiding en metamfetamien behandeling blootgestel was. Addisionele proteine wat deur die kombinasie behandeling geaffekteer is in die buitenste subarea van die nukleus akkumbens sluit ‘malate dehydrogenase’, ‘V-type proton ATPase subunit E1’, ‘beta-synuclein’, ‘brevican core protein’, ‘eukaryotic translation initiation factor 4H’, ‘histidine triad nucleotide binding protein 1’ en ‘stress-induced phosphoprotein’ in. Additionele proteine geaffekteer in die middelste subarea van die nukleus akkumbens sluit ‘thymosin beta-4’, ‘calretinin’, ‘Arpp-21 protein’, ‘alpha-synuclein’, ‘ubiquitin carboxylterminal hydrolase isozyme L1’, ‘cytochrome c’, ‘brain acid soluble protein 1’, ‘prosaposin’ en ‘stress-induced phosphoprotein 1’ in. Vanuit ‘n gedrags benadering deur die gebruik van metamfetamien geinduseerde plek voorkeur het moederlike skeiding nie diere meer vatbaar gemaak vir die effekte van metamfetamien nie, maar die protein data wys wel dat vroeë lewens stres ‘n rol speel deur dat meer proteine geaffekteer word deur die kombinasie van moederlike skeiding gevolg deur later metamfetamien toediening. Ons stel voor dat die molekulêre meganismes waardeur vroeë lewensstres diere meer vatbaar maak vir die verslawende effekte van stimulante behels ‘n komplekse samestelling van sellulêre prosesse in die brein.

Alcohol dependence is a major public health concern. Despite the FDA’s approval of multiple anti-relapse drugs, relapse rates remain unacceptably high. Furthermore, cognitive deficits among chronic drinkers are evident and are suggested to contribute to relapse risk. Current evidence suggests that several critical features of alcoholism and alcohol-associated neurodegeneration are mechanistically linked to glutamatergic actions; specifically, they appear positively affected by glutamatergic inhibition, particularly inhibition via polyamine modulation of a subpopulation of n-methyl-d-aspartate receptors. The current project was designed to evaluate the performance of two putative polyamine modulators (JR-220 and CP-101,606) in a variety of screens designed to identify the potential to reduce withdrawal severity, neurotoxicity and relapse risk. Screens included a complex organotypic screen designed to assess neuroprotective potential (Experiment 1), a simple behavioral screen designed to assess withdrawal severity (Experiment 2) as well as several more complex behavioral screens designed to examine cue-conditioning during withdrawal (Experiment 3), relapse behavior (Experiment 4), stress-associated consumption (Experiment 5) and binge-like consumption (Experiment 6). An additional open field experiment (Experiment 7) was conducted in order to address interpretational issues concerning activity in Experiments 2-6. Finally, as a first step in moving beyond simple screening, we expanded our binge screen to adhere more closely to an established, validated model of binge consumption (Experiment 8). While some interpretational issues were noted, taken together, the results from these experiments provide strong evidence for both drugs as potential pharmacotherapies for alcoholism and further implicate polyamines and NR2B subunits as critical mechanisms in ETOH consumption and withdrawal.

Selective attention towards alcohol-related cues (i.e., “attentional bias”) is thought to reflect increased incentive motivational value of alcohol and alcohol cues acquired through a history of heavy alcohol use, and as such attentional bias is considered to be a clinically relevant factor contributing to alcohol use disorders. This dissertation consists of two studies that investigated specific mechanisms through which attentional bias might serve to promote alcohol abuse. Study 1 compared magnitude of attentional bias in heavy (n = 20) and light (n = 20) drinkers following placebo and two doses of alcohol (0.45 g/kg and 0.65 g/kg). Heavy drinkers displayed significantly greater attentional bias than did moderate drinkers following placebo. However, heavy drinkers displayed a dose-dependent decrease in response to alcohol. Individual differences in attentional bias under placebo were associated with both self-reported and laboratory alcohol consumption, yet bias following alcohol administration did not predict either measure of consumption. These findings suggest that attentional bias is strongest before a drinking episode begins, and as such might be most influential in terms of initiation of alcohol consumption. Study 2 addressed theoretical accounts regarding potential reciprocal interactions between attentional bias and inhibitory control that might promote excessive alcohol consumption. Fifty drinkers performed a measure of attentional bias and a novel task that measures the degree to which alcohol-related stimuli can increase behavioral activation and reduce the ability to inhibit inappropriate responses. As hypothesized, inhibitory failures were significantly greater following alcohol images compared to neutral images. Further, heightened attentional bias was associated with greater response activation following alcohol images. These findings suggest that alcohol stimuli serve to disrupt mechanisms of behavioral control, and that heightened attentional bias is associated with greater disruption of control mechanisms following alcohol images. Taken together, these studies provide strong evidence of an association between attentional bias in sober individuals and alcohol consumption, suggesting a pronounced role of attentional bias in initiation of consumption. Further, findings show that attention to alcohol cues can serve to disrupt mechanisms of inhibitory control that might be necessary to regulate drinking behavior, suggesting a potential means through which attentional bias might promote consumption.

<p>Studiens syfte var att försöka belysa två sätt att se på missbruk (biologisk och psykosocial) som dominerar i missbruksdebatten i dagens Sverige. Vår avsikt var att kartlägga vilket synsätt socialsekreterarna inom missbruksvården har och hur deras synsätt påverkar vilken behandling deras klienter får.</p><p>Våra huvudfrågeställningar var - vilka synsätt har de utredande socialsekreterarna? Kan socialsekreterarnas olika synsätt på missbruk påverka val av behandlingsmetod för klienter? För att kunna få svar på våra frågeställningar tog vi hjälp av två underfrågeställningar. Dessa var - vilka kunskaper har socialsekreterarna om den senaste hjärnforskningen och om psykosociala förklaringsmodeller? Går det att kombinera dessa två olika synsätt?</p><p>Metoden vi använde var kvalitativa halvstrukturerade intervjuer med fem socialarbetare. Resultaten analyserades med hjälp av meningskoncentrering och en meningstematisering och utifrån våra valda teoretiska utgångspunkter – socialkonstruktivism, Durkheims begrepp ”sociala fakta” samt Berglinds handlingsteori. Resultaten visade att valet av respektive sätt att se på missbruk inte hade någon påverkan på valet av behandling. Dessutom visade vår studie att sättet att se på missbruk bland de fem intervjupersonerna vi träffade var ganska lika.</p>

Adolescent substance abuse represents a complex, difficult challenge in the United States. Substance addiction research requires rich contextualization that takes into account individual, familial, and community experiences. This project focuses on how adolescent girls' substance use interacts with risk and vulnerability. More specifically, how the social and biological body influences substance initiation and how local contexts and constraints effects recovery from addiction. The sample includes adolescent girls who are enrolled in substance abuse treatment programs. The methodological approach encompasses a mixture of quantitative and qualitative, including analysis of a nation-wide dataset, narrative interviews, participant observation, and case following. While the quantitative analysis was with the nation-wide dataset, the qualitative data are derived from a sample of adolescent girls in Tucson, Arizona. Risk is assessed along three axes, biocultural, familial, and structural. Biocultural risk examines the influence that an early pubertal developmental trajectory has on substance initiation. Familial risk analyzes how the culture and habitus of the family affects youth initiation of substance use. Structural risk highlights the continued vulnerability that youth who are raised in the `system' face and specifically their challenges to recovery after substance abuse treatment. Findings from the nation-wide sample include a significant relationship between pubertal timing and age of onset of substance use. In the Tucson sample, familial immersion in substance use was so extensive that girls were not only expected to begin using but also initiation of use became a 'rite of passage' within the family. Finally this research documents the unintended role the child welfare system plays as a structural impediment to girls' recovery from substance abuse.

<p>This dissertation explores the ways in which British popular novels of the eighteenth century functioned as commodities. "Novel Addiction", the title of this dissertation has a double meaning: Addiction was a new conceptual framework developed during the eighteenth century in order to manage the increasing anxiety brought upon the culture of consumption, and the novel, one of the most popular commodities of the same period, was addictive. Both as successful commodities and efficient cultural agents, popular novels that were categorized as the sentimental or the gothic participated in the process of creating and disseminating models of addiction that warranted perpetual discipline. However, this discipline does not aim at preventing or eliminating addiction. It rather manages addiction as "habit" in a way that guarantees proliferation of the market economy. By employing the framework of addiction, I intend to reconfigure the role of the novel in the construction of individual and collective models of consumption-oriented subjectivity. </p><p>The first chapter begins with Eliza Haywood's Present for Women Addicted to Drinking where the author proposes novel-reading as the best cure for alcohol addiction, which allows me to explore a parallel between the phenomenon called the "gin craze" and the proliferation of print commodities. The second and third chapter discuss the sentimental novel and the gothic novel respectively focusing on the characteristics of each genre that make them addictive. The fourth and final chapter discusses Jane Austen's Northanger Abbey and Sense and Sensibility, which address and attempt to manage "novel addiction," a problem posed by the popular novels of her contemporaries.</p> / Dissertation

Les récompenses possèdent plusieurs fonctions importantes, liées au plaisir, à la motivation et à l'apprentissage, qui façonnent notre comportement au quotidien. Il est aujourd'hui bien établi que ces fonctions sont prises en charge par un ensemble de régions cérébrales appelé " système de récompense ", dont la perturbation peut générer des comportements inadaptés tels que l'addiction. Néanmoins, toutes les récompenses ne sont pas équivalentes, et il n'y a pas lieu de penser que le cerveau répond de façon identique à chacune d'entre elles. Nous avons testé cette hypothèse à l'aide de l'Imagerie par Résonance Magnétique fonctionnelle (IRMf), en adoptant trois angles d'approche différents. Une première expérience s'est concentrée sur la distinction entre récompenses primaires (i.e. ancestrales et concrètes) et secondaires (i.e. évoluées et abstraites), étudiée ici à travers l'exemple des images érotiques et de l'argent. En plus d'un réseau cérébral activé en commun par ces récompenses, nos résultats ont montré une dissociation au sein du cortex orbitofrontal (OFC), recruté spécifiquement dans sa partie postérieure par les récompenses primaires, et spécifiquement dans sa partie antérieure par les récompenses secondaires. Ce résultat soutient l'idée générale d'un gradient de complexité croissante le long de l'axe postéro-antérieur de l'OFC. Dans la deuxième étude, nous avons comparé, au moyen d'une approche méta-analytique quantitative, les activités cérébrales rapportées dans la littérature en réponse à des gains monétaires, des goûts plaisants et des stimuli érotiques visuels. Les résultats obtenus étayent les conclusions de la première étude, et confirment parallèlement l'existence de réponses cérébrales spécifiques à chaque type de récompense. Enfin, dans la troisième étude, nous nous sommes intéressés au jeu pathologique, en formulant l'hypothèse d'un déséquilibre de la sensibilité aux récompenses monétaires versus non-monétaires. Les résultats obtenus confortent cette prédiction, en suggérant principalement une perturbation du traitement des récompenses non-monétaires dans le striatum ventral des joueurs. Dans l'ensemble, ces résultats apportent un éclairage nouveau sur l'architecture fonctionnelle du système de récompense, à la fois chez des individus sains et des individus joueurs pathologiques

Darbe nagrinėjama priklausomų nuo psichoaktyviųjų medžiagų asmenų gyvenimo kokybė: psichologinė gerovė (pozityvios gerovės pojūtis, savikontrolė, bendrasis sveikatingumas, gyvybingumas, nerimas, depresiška nuotaika), kasdienio gyvenimo fizinė sveikata, psichologinis kūno įvaizdis ir išvaizda, socialiniai ir asmeniniai santykiai, aplinka ir materialiniai ištekliai. Tyrimo tikslas - atlikti priklausomų nuo psichoaktyviųjų medžiagų asmenų, baigusių Lietuvos priklausomybės ligų reabilitacijos centrų ilgalaikes programas, gyvenimo kokybės analizę. Naudotos metodikos: Psichologinės gerovės klausimynas, Pasaulio sveikatos organizacijos Gyvenimo kokybės klausimynas (WHOQOL-BREF). Tyrime dalyvavo 86 ilgalaikę PRP (priklausomybių reabilitacinę programą) baigę asmenys: 68 vyrai ir 17 moterų bei 1 nenurodęs savo lyties asmuo, kurių amžius yra nuo nuo 19 iki 51 metų. Duomenų analizė parodė, kad PRP programą baigusių asmenų, palyginus su reabilitacijos bendruomenėje besigydančiais asmenimis, gyvenimo kokybė yra labiau pozityvi: a) jų geresnė psichologinė gerovė – jie jaučia mažiau nerimo, depresiškos nuotaikos; jaučia turintys daugiau savikontrolės, gyvybingumo; jų yra didesnis pozityvios gerovės pojūtis bei bendrasis sveikatingumas; b) jie savo gyvenimo kokybės visumą bei sveikatos būklę suvokia kaip geresnes; c) jie geriau vertina kasdieninio gyvenimo fizinę sveikatą, socialinius ir asmeninius santykius, aplinką ir materialinius išteklius. PRP programą baigusių asmenų gyvenimo kokybė... [toliau žr. visą tekstą] / The thesis analyses the quality of life of the people with addictive disorders. The quality of life includes their psychological well-being (positive sensation of well-being, self-control, general health, viability, anxiety, and depressed mood), everyday physical health, psychological body image and appearance, social and personal relationships, physical environment and financial resources. The goal of this study was to perform the analysis of the quality of life of the people who have finished long-term addiction rehabilitation programmes in Lithuanian therapeutic communities. The following instruments were used: Psychological General Well-being Schedule, WHO Quality of Life Questionnaire (WHOQOL-BREF). 86 residents of therapeutic communities who have finished a long term ARP (the Addiction Rehabilitation Programme), i.e. 68 men and 17 women and 1 person of an unidentified gender with age ranging from 19 to 51 participated in this study. The data analysis showed that the quality of life of the people who have finished the ARP programme compared to the patients in the same rehabilitation is more positive: a) their psychological well-being is better - they feel less anxiety, depressed mood; they feel more self-control, vitality; they have a greater sensation of positive well-being and general health; b) they perceive their whole quality of life and health status as better; c) they have a better assessment of their everyday physical health, social and personal relationships... [to full text]

Title: ”… Then came the realization that I was just like them. That I have a gambling addiction…” This is a qualitative study of four former gamblers and their experience of getting out of the gambling addiction. The study is about how individuals have overcome a gambling addiction. The purpose of this study is to examine the social processes and factors that are of importance when overcoming a gambling addiction. In addition, the study focuses on how individuals experience the change from gambling addiction to a life free of that addiction. In this thesis, I conducted a qualitative study in the form of semi-structured interviews with four former gamblers. The theoretical approach concentrated on Ebaugh’s (1988) role exit theory and Giddens’ (2005) identity formation theory has been used to illustrate the interviewees' experiences of gambling addiction and their identity as addiction free. The study shows that the gambling addiction has brought economic, social and health-related impacts and some of these aspects still exist today. The exit out of a gambling addiction has been a process with different phases and events where the process for some has been incrementally with relapses during the journey. Based on my results, the changing process appears to consist of parallel turning points where different and more significant events give rise to role exit. The study shows the need of continuous social support in combination with gambling association support efforts and the gamblers’ own insight, motivation and freedom of action. It appears that the interviewed have accepted their role that they had left behind and they take careful consideration to the past and the future and try to make more conscious choices and build their new identity. This is done by actions and re- evaluations of themselves and their world. It is based on their lives, by their own choices. However, these choices seem to be limited by conditions that occur in the interaction with the environment, social norms and social situations.

Bemötandet inom missbruks- och beroendevården är oerhört viktigt för att klienter ska vilja motta stöd från de som utför vården, och mötet mellan behandlare och klient kan vara ett första steg i rätt riktning för klienten. Syftet med den här studien var att undersöka hur personalen bemöter vuxna klienter med missbruks eller beroendeproblematik. För att besvara studiens syfte och frågeställningar genomfördes studien med en kvalitativ ansats. Materialinsamling har skett genom sju stycken semistrukturerade intervjuer, och analyserades sedan genom kvalitativ innehållsanalys. Studiens teoretiska tolkningsram utgår från Goffmans dramaturgiska perspektiv. Resultatet i studien visar att bemötandet inom missbruks och beroendevården bör kännetecknas av ett kunskapsbaserat och respektfullt förhållningssätt och signalera mänsklig värme, samt grundas på ett individanpassat bemötande med tro på individers egna förmågor. Resultatet visade även på försvårande faktorer i bemötandet, nämligen klientens sjukdomsbild, förnekelse, motstånd och den asymmetriska maktrelationen. / The treatment of clients within abuse and addiction care is extremely important for clients to want to receive support from those who perform care, and the meeting between councellor/therapist and client can be a first step in the right direction for the client. The purpose of this study was to examine how the staff treats adult clients with substance abuse or addiction. To answer the study's purpose and issues conducted the study with a qualitative approach. Materials Collection has been done through seven semi-structured interviews, and then analyzed by qualitative content analysis. Theoretical study of interpretation based on Goffman´s dramaturgical perspective. The results of the study show that the hospitality of substance abuse and addiction services should be characterized by knowledge-based and respectful attitude and signal the human warmth, and it should be based on an individualized treatment with the belief in the individual's own abilities. The result also showed the aggravating factors in the plea, namely the client's illness, denial, resistance, and the asymmetrical power relationship.