Roles of forced nicotine exposure and Comt gene disruption in the development of addiction-related behavioural and neurochemical changes in mice

Activation of midbrain dopamine systems is thought to be critically involved in the addictive properties of abused substances. Drugs of abuse increase dopamine release in the nucleus accumbens and dorsal striatum, which are the target areas of mesolimbic and nigrostriatal dopamine pathways, respectively. Dopamine release in the nucleus accumbens is thought to mediate the attribution of incentive salience to rewards, and dorsal striatal dopamine release is involved in habit formation. In addition, changes in the function of prefrontal cortex (PFC), the target area of mesocortical dopamine pathway, may skew information processing and memory formation such that the addict pays an abnormal amount of attention to drug-related cues. In this study, we wanted to explore how long-term forced oral nicotine exposure or the lack of catechol-O-methyltransferase (COMT), one of the dopamine metabolizing enzymes, would affect the functioning of these pathways. We also wanted to find out how the forced nicotine exposure or the lack of COMT would affect the consumption of nicotine, alcohol, or cocaine. First, we studied the effect of forced chronic nicotine exposure on the sensitivity of dopamine D2-like autoreceptors in microdialysis and locomotor activity experiments. We found that the sensitivity of these receptors was unchanged after forced oral nicotine exposure, although an increase in the sensitivity was observed in mice treated with intermittent nicotine injections twice daily for 10 days. Thus, the effect of nicotine treatment on dopamine autoreceptor sensitivity depends on the route, frequency, and time course of drug administration. Second, we investigated whether the forced oral nicotine exposure would affect the reinforcing properties of nicotine injections. The chronic nicotine exposure did not significantly affect the development of conditioned place preference to nicotine. In the intravenous self-administration paradigm, however, the nicotine-exposed animals self-administered nicotine at a lower unit dose than the control animals, indicating that their sensitivity to the reinforcing effects of nicotine was enhanced. Next, we wanted to study whether the Comt gene knock-out animals would be a suitable model to study alcohol and cocaine consumption or addiction. Although previous work had shown male Comt knock-out mice to be less sensitive to the locomotor-activating effects of cocaine, the present study found that the lack of COMT did not affect the consumption of cocaine solutions or the development of cocaine-induced place preference. However, the present work did find that male Comt knock-out mice, but not female knock-out mice, consumed ethanol more avidly than their wild-type littermates. This finding suggests that COMT may be one of the factors, albeit not a primary one, contributing to the risk of alcoholism. Last, we explored the effect of COMT deficiency on dorsal striatal, accumbal, and prefrontal cortical dopamine metabolism under no-net-flux conditions and under levodopa load in freely-moving mice. The lack of COMT did not affect the extracellular dopamine concentrations under baseline conditions in any of the brain areas studied. In the prefrontal cortex, the dopamine levels remained high for a prolonged time after levodopa treatment in male, but not female, Comt knock-out mice. COMT deficiency induced accumulation of 3,4-dihydroxyphenylacetic acid, which increased further under levodopa load. Homovanillic acid was not detectable in Comt knock-out animals either under baseline conditions or after levodopa treatment. Taken together, the present results show that although forced chronic oral nicotine exposure affects the reinforcing properties of self-administered nicotine, it is not an addiction model itself. COMT seems to play a minor role in dopamine metabolism and in the development of addiction under baseline conditions, indicating that dopamine function in the brain is well-protected from perturbation. However, the role of COMT becomes more important when the dopaminergic system is challenged, such as by pharmacological manipulation.

Essays on Economic Integration and Labour Demand

This dissertation consists of an introductory section and three essays investigating the effects of economic integration on labour demand by using theoretical models and by empirical analysis. The essays adopt an intra-industry trade approach to specify a theoretical framework of estimation for determining the effects of economic integration on employment. In all the essays the empirical aim is to explore the labour demand consequences of European integration. The first essay analyzes how labour-demand elasticities with own price have changed during the process of economic integration. As a theoretical result, intensified trade competition increases labour-demand elasticity, whereas better advantage of economies of scale decreases labour-demand elasticity by decreasing the elasticity of substitution between differentiated products. Furthermore, if integration gives rise to an increase in input-substitutability and/or outsourcing activities, labour demand will become more elastic. Using data from the manufacturing sector from 1975 to 2002, the empirical results provide support for the hypothesis that European integration has contributed to increased elasticities of total labour demand in Finland. The second essay analyzes how economic integration affects the impact of welfare poli-cies on employment. The essay considers the viability of financing the public sector, i.e. public consumption and social security expenses, by general labour taxation in an economy which has become more integrated into international product markets. The theoretical results of the second essay indicate that, as increased trade competition crowds out better economies of scale, it becomes more costly to maintain welfare systems financed by labour taxation. Using data from European countries for the years 1975 to 2004, the empirical results provide inconsistent evidence for the hypothesis that economic integration has contributed to the distortion effects of welfare policies on employment. The third essay analyzes the impact of profit sharing on employment as a way to introduce wage flexibility into the process of economic integration. The results of the essay suggest that, in theory, the effects of economic integration on the impact of profit sharing on employment clearly depend on a trade-off between intensified competition and better advantage of economies of scale. If product market competition increases, the ability of profit sharing to improve employment through economic integration increases with moderated wages. While, the economic integration associating with market power in turn decrease the possibilities of profit sharing with higher wages to improve employment. Using data from the manufacturing sector for the years 1996 to 2004, the empirical results show that profit-sharing has a positive impact on employment during the process of European integration, but can have ambiguous effects on the stability of employment in Finland.

Studies on Wage Differentials and Labour Market Transitions

This thesis consists of four studies. The first study examines wage differentials between women and men in the Finnish manufacturing sector. A matched employer-employee data set is used to decompose the overall gender wage gap into the contributions of sex differences in human capital, labour market segregation, and residual within-job wage differentials. The topic of the second study is the relationship between the extended unemployment benefits and labour market transitions of older workers. The analysis exploits a quasi-experimental setting caused by a change in the law that raised the eligibility age of workers benefiting from extended benefits. Roughly half of the unemployed workers with extended benefits are estimated to be effectively withdrawn from labour market search. The risk of unemployment declined and the re-employment probability increased among the age groups directly affected by the reform. The third study provides an empirical analysis of a structural equilibrium search model. Estimation results from various model specifications are compared and discussed. The last study is a methodological study where the difficulties of interpreting the results of competing risks hazard models are discussed and a solution for a particular class of models is proposed. It is argued that a common practice of reporting the results of qualitative response models in terms of marginal effects is also useful in the context of competing risks duration models.

Spirometric studies on the adult general population of Helsinki : bronchodilation responses, determinants, and intrasession repeatability of FEV1, FEV6, FVC, and forced expiratory time

Spirometry is the most widely used lung function test in the world. It is fundamental in diagnostic and functional evaluation of various pulmonary diseases. In the studies described in this thesis, the spirometric assessment of reversibility of bronchial obstruction, its determinants, and variation features are described in a general population sample from Helsinki, Finland. This study is a part of the FinEsS study, which is a collaborative study of clinical epidemiology of respiratory health between Finland (Fin), Estonia (Es), and Sweden (S). Asthma and chronic obstructive pulmonary disease (COPD) constitute the two major obstructive airways diseases. The prevalence of asthma has increased, with around 6% of the population in Helsinki reporting physician-diagnosed asthma. The main cause of COPD is smoking with changes in smoking habits in the population affecting its prevalence with a delay. Whereas airway obstruction in asthma is by definition reversible, COPD is characterized by fixed obstruction. Cough and sputum production, the first symptoms of COPD, are often misinterpreted for smokers cough and not recognized as first signs of a chronic illness. Therefore COPD is widely underdiagnosed. More extensive use of spirometry in primary care is advocated to focus smoking cessation interventions on populations at risk. The use of forced expiratory volume in six seconds (FEV6) instead of forced vital capacity (FVC) has been suggested to enable office spirometry to be used in earlier detection of airflow limitation. Despite being a widely accepted standard method of assessment of lung function, the methodology and interpretation of spirometry are constantly developing. In 2005, the ATS/ERS Task Force issued a joint statement which endorsed the 12% and 200 ml thresholds for significant change in forced expiratory volume in one second (FEV1) or FVC during bronchodilation testing, but included the notion that in cases where only FVC improves it should be verified that this is not caused by a longer exhalation time in post-bronchodilator spirometry. This elicited new interest in the assessment of forced expiratory time (FET), a spirometric variable not usually reported or used in assessment. In this population sample, we examined FET and found it to be on average 10.7 (SD 4.3) s and to increase with ageing and airflow limitation in spirometry. The intrasession repeatability of FET was the poorest of the spirometric variables assessed. Based on the intrasession repeatability, a limit for significant change of 3 s was suggested for FET during bronchodilation testing. FEV6 was found to perform equally well as FVC in the population and in a subgroup of subjects with airways obstruction. In the bronchodilation test, decreases were frequently observed in FEV1 and particularly in FVC. The limit of significant increase based on the 95th percentile of the population sample was 9% for FEV1 and 6% for FEV6 and FVC; these are slightly lower than the current limits for single bronchodilation tests (ATS/ERS guidelines). FEV6 was proven as a valid alternative to FVC also in the bronchodilation test and would remove the need to control duration of exhalation during the spirometric bronchodilation test.

Retirement Transition and Well-being : A 16-year Longitudinal Study

The ageing of the labour force and falling employment rates have forced policy makers in industrialized countries to find means of increasing the well-being of older workers and of lengthening their work careers. The main objective of this thesis was to study longitudinally how health, functional capacity, subjective well-being, and lifestyle change as people grow older, and what effect retirement has on these factors and on their relationships. The present study is a follow-up questionnaire study of Finnish municipal workers, conducted in 1981 to 1997 at the Finnish Institute of Occupational Health. In 1981, a postal questionnaire was sent to 7344 municipal workers in different parts of Finland. The respondents were born between 1923 and 1937. A total of 6257 persons responded to the first questionnaire. In the end, a total of 3817 persons had responded to all four (1981, 1985, 1992, 1997) questionnaires. (The response rate was 69% of the living participants). Cross-tabulations, comparison of means, logistic regression analyses and general linear models with repeated measures were used to derive the results. The transition from work life to retirement, and the following years as a pensioner were associated with many changes. Involvement in various activities increased during the transition stage but later decreased to the previous level. Physical exercise was an exception: it became increasingly popular over the years. Perceived health improved markedly from the working stage to the retirement transition stage, even though morbidity increased steadily during the follow-up. On the other hand, functional capacity decreased over the follow-up, especially among those who were occupationally active until the retirement stage. Subjective well-being remained stable during the follow-up period. There were, however, great differences based on the type of work, favouring those whose work had been mental in nature. The impact of activity level on maintaining well-being became greater during the follow-up, whereas the effect of physical functioning diminished. Good physical functioning and an active life-style contributed to staying on at work until normal retirement age. Also work-related factors, i.e. possibilities for development and influence at work, responsibility for others, meaningful work, and satisfaction with working time arrangements were positively related to continuing working. The transition from work to retirement had a positive impact on a person s health and functional capacity. The study results support the view that it should be possible to ease one s work pace during the last years of a work career. This might lower the threshold between work and retirement and convince people that there will still be time to enjoy retirement also a few years later.

Modern Societal Impulses and their Nordic Manifestations : On Emancipation and Constraint in Societal Development

The 1980s and the early 1990s have proved to be an important turning point in the history of the Nordic welfare states. After this breaking point, the Nordic social order has been built upon a new foundation. This study shows that the new order is mainly built upon new hierarchies and control mechanisms that have been developed consistently through economic and labour market policy measures. During the post-war period Nordic welfare states to an increasing extent created equality of opportunity and scope for agency among people. Public social services were available for all and the tax-benefit system maintained a level income distribution. During this golden era of Nordic welfare state, the scope for agency was, however, limited by social structures. Public institutions and law tended to categorize people according to their life circumstances ascribing them a predefined role. In the 1980s and 1990s this collectivist social order began to mature and it became subject to political renegotiation. Signs of a new social order in the Nordic countries have included the liberation of the financial markets, the privatizing of public functions and redefining the role of the public sector. It is now possible to reassess the ideological foundations of this new order. As a contrast to widely used political rhetoric, the foundation of the new order has not been the ideas of individual freedom or choice. Instead, the most important aim appears to have been to control and direct people to act in accordance with the rules of the market. The various levels of government and the social security system have been redirected to serve this goal. Instead of being a mechanism for redistributing income, the Nordic social security system has been geared towards creating new hierarchies on the Nordic labour markets. During the past decades, conditions for receiving income support and unemployment benefit have been tightened in all Nordic countries. As a consequence, people have been forced to accept deteriorating terms and conditions on the labour market. Country-specific variations exist, however: in sum Sweden has been most conservative, Denmark most innovative and Finland most radical in reforming labour market policy. The new hierarchies on the labour market have co-incided with slow or non-existent growth of real wages and with a strong growth of the share of capital income. Slow growth of real wages has kept inflation low and thus secured the value of capital. Societal development has thus progressed from equality of opportunity during the age of the welfare states towards a hierarchical social order where the majority of people face increasing constraints and where a fortunate minority enjoys prosperity and security.

Doing marriage and parenthood: The division of household labour across two life course events

The current study is a longitudinal investigation into changes in the division of household labour across transitions to marriage and parenthood in the UK. Previous research has noted a more traditional division of household labour, with women performing the majority of housework, amongst spouses and couples with children. However, the bulk of this work has been cross-sectional in nature. The few longitudinal studies that have been carried out have been rather ambiguous about the effect of marriage and parenthood on the division of housework. Theoretically, this study draws on gender construction theory. The key premise of this theory is that gender is something that is performed and created in interaction, and, as a result, something fluid and flexible rather than fixed and stable. The idea that couples ‘do gender’ through housework has been a major theoretical breakthrough. Gender-neutral explanations of the division of household labour, positing rational acting individuals, have failed to explicate why women continue to perform an unequal share of housework, regardless of socio-economic status. Contrastingly, gender construction theory situates gender as the key process in dividing household labour. By performing and avoiding certain housework chores, couples fulfill social norms of what it means to be a man and a woman although, given the emphasis on human agency in producing and contesting gender, couples are able to negotiate alternative gender roles which, in turn, feed back into the structure of social norms in an ever-changing societal landscape. This study adds extra depth to the doing gender approach by testing whether or not couples negotiate specific conjugal and parent roles in terms of the division of household labour. Both transitions hypothesise a more traditional division of household labour. Data comes from the British Household Panel Survey, a large, nationally representative quantitative survey that has been carried out annually since 1991. Here, data tracks the same 776 couples at two separate time points – 1996 and 2005. OLS regression is used to test whether or not transitions to marriage and parenthood have a significant impact on the division of household labour whilst controlling for host of relevant socio-economic factors. Results indicate that marriage has no significant effect on how couples partition housework. Those couples making the transition from cohabitation to marriage do not show significant changes in housework arrangements from those couples who remain cohabiting in both waves. On the other hand, becoming parents does lead to a more traditional division of household labour whilst controlling for socio-economic factors which accompany the move to parenthood. There is then some evidence that couples use the site of household labour to ‘do parenthood’ and generate identities which both use and inform socially prescribed notions of what it means to be a mother and a father. Support for socio-economic explanations of the division of household labour was mixed although it remains clear that they, alone, cannot explain how households divide housework.

Doing marriage and parenthood: The division of household labour across two life course events

The current study is a longitudinal investigation into changes in the division of household labour across transitions to marriage and parenthood in the UK. Previous research has noted a more traditional division of household labour, with women performing the majority of housework, amongst spouses and couples with children. However, the bulk of this work has been cross-sectional in nature. The few longitudinal studies that have been carried out have been rather ambiguous about the effect of marriage and parenthood on the division of housework. Theoretically, this study draws on gender construction theory. The key premise of this theory is that gender is something that is performed and created in interaction, and, as a result, something fluid and flexible rather than fixed and stable. The idea that couples 'do gender' through housework has been a major theoretical breakthrough. Gender-neutral explanations of the division of household labour, positing rational acting individuals, have failed to explicate why women continue to perform an unequal share of housework, regardless of socioeconomic status. Contrastingly, gender construction theory situates gender as the key process in dividing household labour. By performing and avoiding certain housework chores, couples fulfill social norms of what it means to be a man and a woman although, given the emphasis on human agency in producing and contesting gender, couples are able to negotiate alternative gender roles which, in turn, feed back into the structure of social norms in an ever-changing societal landscape. This study adds extra depth to the doing gender approach by testing whether or not couples negotiate specific conjugal and parent roles in terms of the division of household labour. Both transitions hypothesise a more traditional division of household labour. Data comes from the British Household Panel Survey, a large, nationally representative quantitative survey that has been carried out annually since 1991. Here, data tracks the same 776 couples at two separate time points - 1996 and 2005. OLS regression is used to test whether or not transitions to marriage and parenthood have a significant impact on the division of household labour whilst controlling for host of relevant socio-economic factors. Results indicate that marriage has no significant effect on how couples partition housework. Those couples making the transition from cohabitation to marriage do not show significant changes in housework arrangements from those couples who remain cohabiting in both waves. On the other hand, becoming parents does lead to a more traditional division of household labour whilst controlling for socio-economic factors which accompany the move to parenthood. There is then some evidence that couples use the site of household labour to 'do parenthood' and generate identities which both use and inform socially prescribed notions of what it means to be a mother and a father. Support for socio-economic explanations of the division of household labour was mixed although it remains clear that they, alone, cannot explain how households divide housework.

Domestic labour relations in India : Vulnerability and gendered life courses in Jaipur

This study explores labour relations between domestic workers and employers in India. It is based on interviews with both employers and workers, and ethnographically oriented field work in Jaipur, carried out in 2004-2007. Combining development studies with gender studies, labour studies, and childhood studies, it asks how labour relations between domestic workers and employers are formed in Jaipur, and how female domestic workers trajectories are created. Focusing on female part-time maids and live-in work arrangements, the study analyses children s work in the context of overall work force, not in isolation from it. Drawing on feminist Marxism, domestic labour relations are seen as an arena of struggle. The study takes an empirical approach, showing class through empiria and shows how paid domestic work is structured and stratified through intersecting hierarchies of class, caste, gender, age, ethnicity and religion. The importance of class in domestic labour relations is reiterated, but that of caste, so often downplayed by employers, is also emphasized. Domestic workers are crucial to the functioning of middle and upper middle class households, but their function is not just utilitarian. Through them working women and housewives are able to maintain purity and reproduce class disctinctions, both between poor and middle classes and lower and upper middle classes. Despite commodification of work relations, traditional elements of service relationships have been retained, particularly through maternalist practices such as gift giving, creating a peculiar blend of traditional and market practices. Whilst employers of part-time workers purchase services in a segmented market from a range of workers for specific, traditional live-in workers are also hired to serve employers round the clock. Employers and workers grudgingly acknowledged their dependence on one another, employers seeking various strategies to manage fear of servant crime, such as the hiring of children or not employing live-in workers in dual-earning households. Paid domestic work carries a heavy stigma and provide no entry to other jobs. It is transmitted from mothers to daughters and working girls were often the main income providers in their families. The diversity of working conditions is analysed through a continuum of vulnerability, generic live-in workers, particularly children and unmarried young women with no close family in Jaipur, being the most vulnerable and experienced part-time workers the least vulnerable. Whilst terms of employment are negotiated informally and individually, some informal standards regarding salary and days off existed for maids. However, employers maintain that workings conditions are a matter of individual, moral choice. Their reluctance to view their role as that of employers and the workers as their employees is one of the main stumbling blocks in the way of improved working conditions. Key words: paid domestic work, India, children s work, class, caste, gender, life course

Essays on labour demand and wage formation

The first essay in this thesis is on gender wage differentials among manufacturing sector white-collar workers. The wage differential is decomposed into firm, job (within-firm) and individ-ual-level components. Job-level gender segregation explains over half of the gap, while firm-level segregation is not important. After controlling for firm, job and individual characteristics, the remaining unexplained wage cap to the advantage of men is six per cent of men s mean wage. In the second essay, I study how the business cycle and gender affect the distribution of the earnings losses of displaced workers. The negative effect of displacement is large, persistent and strongest in the lowest earnings deciles. The effect is larger in a recession than in a recov-ery period, and in all periods women s earnings drop more than men s earnings. The third essay shows that the transition from steady employment to disability pension de-pends on the stringency of medical screening and the degree of experience-rating of pension costs applied to the employer. The fact that firms have to bear part of the cost of employees disability pension costs lowers both the incidence of long sick leave periods and the probabil-ity that sick leave ends in a disability pension. The fourth and fifth essays are studies on the employment, wage and profit effects of a re-gional payroll tax cut experiment conducted in northern and eastern Finland. The results show no statistically significant effect on any of the response variables.