Cocaine (CA) exposure during pregnancy causes long-lasting negative effects on fetal brain development and eventually results in motor dysfunction or changes in learning and memory performance. £^-amino-butyric acid (GABA) is the primary inhibitory neurotransmitter in the adult brain and undergo a switch from excitatory to inhibitory during early postnatal period. The excitatory/inhibitory switch is resulted in the relative temporal expression of K+-Cl- cotransporter 2 (KCC2). GABA is the neurotransmitter in the rat was born from excitement to inhibition and until the growth of thirty days have completely inhibitory. Here we test the effect of CA prenatal exposure on the expression of KCC2 in prefrontal cortex (recognition), hippocampus (memory), VTA (reward) and nucleus accumbens (reward). Protein expression profile of control or prenatal CA treated groups were evaluated by western blot in 2 days interval from postnatal day (PND) 8 to 30. The expression of KCC2 was time-dependently enhanced from PND 8 and reaches its maximal expression around PND 18 in prenatal CA exposure groups. The time-dependent profile of KCC2 expression in prefrontal cortex and NAc was significantly delayed in prenatal CA exposure group. We then correlate the KCC2 expression and the cocaine sensitivity by locomotor activity assay. We found group A shows a higher sensitivity to cocaine than group B in control rats. Surprisingly, group A of prenatal cocaine reduce the sensitive to cocaine to a similar extend like group B in control rats, suggesting prenatal exposure of cocaine might enhance the KCC2 expression. Furthermore, age range of A group (PND 22~27) and B group (PND 29~34) to repeated cocaine exposure resulted in up-regulation of KCC2 expression in B group earlier than A group. We found that the KCC2 expressions of repeated cocaine exposure in B group were higher than A group. In other words, in the B group, the inhibitory effect of GABA was significant and the locomotor activity was relatively slow. Therefore, the A group was more easy be cocaine addiction than B group. We next explore the signaling mechanism underlying cocaine exposure-induced KCC2 expression inhibition. Brain slices were incubated with cocaine with or without dopamine receptor antagonists and KCC2 expression was evaluated by western blot. Either SCH23390 (dopamine D1-receptor inhibitor) or eticlopride (dopamine D2-receptor inhibitor) significantly hamper the inhibition of KCC2 expression by cocaine in normal slices. However, only D2 antagonist eticlopride but not SCH23390 is effective reverse cocaine-induced KCC2 expression inhibition. Overall, results from our current studies provide a further insight into the molecular mechanism of cocaine-induced synaptic modification.

published_or_final_version / Public Administration / Master / Master of Social Sciences

Thesis (Ph. D. in Molecular Physiology and Biophysics)--Vanderbilt University, Aug. 2009. / Title from title screen. Includes bibliographical references.

Thesis (Ph. D. in Neuroscience)--Vanderbilt University, Aug. 2009. / Title from title screen. Includes bibliographical references.

Thesis (M.Soc.Sc.)--University of Hong Kong, 1988. / Also available in print.

In writing my thesis, I have thought that some notes from my first seven years' medical work undertaken, as it was, in North China might not prove unacceptable. In the year 1886 I took charge of the Peking Hospital & Dispensary, with some private work outside. The Peking Hospital was an old established institution, well known throughout the capital & some of the districts surrounding it. There was therefore, from the first, a very large attendance of patients residing outside the city walls, as well as those living in the city itself. The great bulk of patients came from the northern province of Chihli, in which the capital is situated, but many came from other provinces and more distant parts of the empire.

INTRODUCTION: With the advent of advanced neuroimaging, strides have been made towards better understanding the cognitive elements necessary for task processing. Resting state functional connectivity assessments using functional magnetic resonance imaging has allowed patient assessments of underlying neural networks in patient populations with variable constraints. Drug addiction, a chronically relapsing disorder, presents many variable constraints. Cellular and molecular changes in neural reward pathway of drug addicted patient populations have advanced, but circuit-level alterations with reward deficits are yet to be completely understood. Resting state functional connectivity investigations in patient populations that use illicit drugs are seen to have repercussions on neural networks. OBJECTIVE: Assess and compare reward-network resting state functional connectivity investigations in patient populations with illicit drug use. METHODS: A meta-analysis of several resting state functional connectivity studies. Patient populations for each study contained an experimental group of drug users with a group of non-drug using controls to assess changes in resting state functional connectivity of the reward network. Studies utilized Diagnostic and Statistical Manuel of Mental disorders, 4th edition, as the basis of diagnosing drug dependence and abuse. A 3 Tesla MRI scanner was utilized to assess the reward pathway of the drug abuse in all experiments with the exception of one group using a 4 Tesla scanner. Band-pass temporal filtering from roughly 0.01 Hz to 0.1 Hz on residual signals was used to obtain low-frequency fluctuations needed for resting state connectivity analyses. Correlation maps were created by computing the correlation coefficients between the blood oxygen level dependent time course from the seed regions and from all other brain voxels. Regions of interest were chosen based on data from databases or previous studies. RESULTS: Four papers found widespread reductions in the connectivity of multiple reward pathway components. Results of these studies are consistent with perspectives suggesting that transition from drug use to addiction is driven by reduced functioning of reward systems and concurrently increased activation of anti-reward systems. Two studies suggested an increase in reward pathway of drug use, suggesting enhanced connectivity within reward and motivation circuits may be interpreted in the perspective of altered incentive salience for drugs and drug-associated stimuli. CONCLUSION: At early stage of experimental data in this field, data interpretation necessitates caution. Small sample sizes, heterogeneous subject groups and variable experimental paradigms may have lead to opposing findings. With certainty, chronic drug use was found to alter reward pathway in patient populations.

O presente trabalho tem como objetivo trazer uma pequena contribuição à resposta que a clínica psicanalítica vem sendo solicitada a dar para a questão da toxicomania e do seu tratamento. Trata-se, pois, de uma pesquisa fundamentalmente teórica, cujas duas grandes partes articulam os temas da Toxicomania e da Transferência psicanalítica. As reflexões teóricas foram ilustradas com os testemunhos de alguns psicanalistas que lidam com toxicômanos. Na primeira parte, buscou-se compreender, mediante algumas referências fundamentais da Metapsicologia freudiana, as principais características da vida psíquica e pulsional do toxicômano. Na segunda parte, dedicada ao problema do tratamento psicanalítico desses pacientes, procurou-se problematizar alguns aspectos específicos, que se apresentam como obstáculos e/ou possibilidades para a constituição de um campo transferencial e os manejos que se fazem necessários para a criação de um espaço analítico, onde possa o toxicômano ser acolhido e escutado em vista de um tratamento analítico. A segunda parte, por sua vez, foi dividida em dois capítulos, o primeiro dos quais aborda a trajetória percorrida por Freud para a elaboração teórica do conceito psicanalítico de transferência, mostrando sua central importância na análise. O segundo trata da novidade clínica que a toxicomania representa e as diversas questões que levanta: a chegada do toxicômano ao analista, suas demandas que geralmente não são de análise , e a posição em que esses pacientes tendem a colocar o analista. Faz-se, ainda, uma referência à complexidade das transferências múltiplas, próprias do tratamento institucional, e ao novo desafio que elas representam para a clínica psicanalítica / The objective of this present study is to give a little contribution to the answer that the psychoanalytic clinic is asked to give to the matter of drug addiction and its treatment. It is indeed a theoretical research, whose two main parts are linked to the matters of drug dependence and psychoanalytic transference. The theoretical reflections were clarified with the testimonies of some psychoanalysts that deaI. with drug dependants. On the part we tried to understand, through some fundamental references of the Freudian Meta psychology, the main characteristics of the psychic and pulsing life of the drug addict. On the second part, we dedicated to the problem of the psychoanalytical treatment of those patients, we tried to raise the problem of some specific aspects that present themselves as obstacles or possibilities for the constitution of a transferential field and the handling necessary for lhe creation of a analytic field, where the drug addict may be guarded and heard so as to be given an analytic treatment. The second part was algo divided into two chapters, the first one deals with the trajectory that Freud went through for a theoretical elaboration of the psychoanalytical concept of the transference thus showing its central importance in the analysis. The second one deals with the clinical news that drug addiction represents and the various problems that it raises; the arrival of the drug dependent to the analyst, his demands -that are not generally related to analysis -and the attitude in which these patients have the tendency of placing the analyst -We still make a reference to the complexity of the multiple transferences inherent to the institutional treatment an to the new challenge that they represent to the psychoanalytical clinic

Magister Psychologiae - MPsych / Substance use addiction is a debilitating and destructive human disorder that affects millions of people worldwide. Of all the provinces in South Africa, the Western Cape has the highest rate of MA use. This highly addictive stimulant, locally known as 'tik', has multiple physiological, psychological, and social effects on the user. The effects are associated with neurocognitive deficits that include deficiencies in working memory and high rates of delay discounting. Current neuropsychopharmacology literature seems to suggest that changes in neurotransmitter functioning and particular brain areas occur that contribute to some of the addictive behaviours associated with chronic MA use. New evidence is emerging that working memory training can help to improve rates of impulsivity in those addicted to MA by strengthening cognitive control. The aim of this project was to establish whether differences in impulse control existed in a sample of 33 male patients at a Western Cape drug rehabilitation centre who received either working memory training with standard drug rehabilitation and or standard drug rehabilitation only. Data was collected with a self-report impulsivity scale (BIS – 11) and analysed using inferential statistics. The results suggest that working memory training, when paired with a standard rehabilitation program, has superior effects in decreasing self-reported rates of impulsivity when compared to standard rehabilitation only. These findings suggest that working memory training may serve as a useful addition to improving impulsivity rates in MA rehabilitation treatment. Further research on a larger scale is required to investigate the findings of this project.

Magister Scientiae (Occupational Therapy) - MSc(OT) / The growing phenomenon of drug abuse has alerted the attention of health professionals, addiction counsellors, school educators, the media and community members. Susceptible sub groups of the population such as adolescents have been seriously affected as addiction destroys their identities, health, daily performance, family structure and ultimately results in social disintegration. Consequently, rehabilitation facilities have been established and addicts are entering the treatment system via referrals from school principals, the judiciary court or desperate parents and family members. Despite this, after having spent a reasonable amount of time and money in rehabilitation centres, relapse rates are significantly high and addicts are returning to treatment. The question was then raised as to whether recurrent relapses were as a result of their occupational needs not being met in treatment. To understand whether the occupational needs of these recovering adolescents are met, a true client-centred approach was employed. A descriptive approach was used within a qualitative research paradigm. The participants that were selected from four drug rehabilitation facilities in the Cape Town Metropolis, included 8 recovering drug addicted adolescents, 2 rehabilitation workers employed at two different facilities, and a sum of 26 parents of recovering addicts. Purposeful sampling was used for the adolescents and rehabilitation workers while convenient sampling was used for the parents. To access the perspectives and perceptions of the participants the researcher used individual semi-structured interviews for the recovering adolescents and drug rehabilitation workers, and focus groups for the parents. The data was analysed thematically using Lincoln & Guba’s (1985) method of qualitative data analysis. All data was managed manually. The objectives of the study explored perceptions of drug addicted adolescents with regard to relapse, to describe the barriers with regard to drug rehabilitation and their occupational needs, to reveal facilitators with reference to the recovery process, and to present suitable strategies which may improve drug treatment practice. Three themes were constructed based on the findings of the study. The themes were: 1) easy to get in, difficult to get out, 2) breakdown on life caused by drug addiction, and 3) moving forward towards recovery. Since adolescence is known as a transitional period characterised by identity development, adolescents are naturally influenced by their social and physical environment, particularly their peer groups at school and in the community. Consequently, adolescents enter treatment with numerous physical, psychological, social, intrapersonal, and legal needs. The constant pursuit of drugs and its lifestyle leads to dysfunction and imbalance in the individual’s daily performances with relapse remaining a common element in the recovery process. The lack of knowledge from participants pertaining to the concept of relapse was perceived as a barrier to recovery. The physical and social environment such as the general availability and accessibility of drugs in adolescent’s community, the unfavourable influence that peers and family relationships play, organisational challenges such as staff handling principles regarding their developmental stage and ineffective communication within the rehabilitation centre, and personal barriers including manipulative and behavioural difficulties, emerged as contra-indicative to the recovery process. Many of the recovering drug addicted adolescents were unable to cope with the array of needs and triggers, and found themselves relapsing and returning to the rehabilitation facility. Among the many facilitators as perceived by the participants, the actual programme at the rehabilitation centre was significant in promoting progress. If it included education groups, where clients are taught about substance abuse, relapse and how to restructure their lifestyle of recovery, it was deemed as beneficial. Another facilitator highlighted by the participants was the involvement of family by incorporating parent support sessions, and an interesting factor suc Recommendations for the study included that adolescents who abuse substances need to be treated very differently to adults or children, and that maintaining communication or a connection with them via aftercare for example, will enable them to sustain their sobriety outside of the rehabilitation facility. Since addiction affects the individual’s identity, roles, and habits on an occupational performance level it is paramount that treatment should be addressed from an occupation-based perspective in collaboration with existing evidence-based addiction models. Occupational therapists are uniquely equipped to deal with these components. h as including spirituality as a resource was raised as valuable in their recovery process.