Glutamatergic Modulation of Cue-Induced Drug-Seeking Behavior in the Rat

The characteristics of drug addiction include compulsive drug use despite negative consequences and re-occurring relapses, returns to drug use after a period of abstinence. Therefore, relapse prevention is one of the major challenges for the treatment of drug addiction. There are three main factors capable of inducing craving for drugs and triggering relapse long after cessation of drug use and dissipation of physical withdrawal signs: stress, re-exposure to the drug, and environmental stimuli (cues) that have been previously associated with drug use. The neurotransmitters dopamine and glutamate have been implicated in the modulation of drug-seeking behavior. The aim of this project was to examine the role of glutamatergic neurotransmission in relapse triggered by conditioned drug-associated stimuli. The focus was on clarifying whether relapse to drug seeking can be attenuated by blockade of glutamate receptors. In addition, as the nucleus accumbens has been proposed to participate in the modulation of drug-seeking behavior, the effects of glutamate receptor blockade in this brain structure on cue-induced relapse were investigated. The studies employed animals models in which rats were trained to press a lever in a test cage to obtain alcohol or intravenous cocaine. Drug availability was paired with distinct olfactory, auditory, or visual stimuli. This phase was followed by extinction training, during which lever presses did not result in the presentation of the drug or the drug-associated stimuli. Extinction training led to a gradual decrease in the number of lever presses during test sessions. Relapse was triggered by presenting the rats with the drug-associated stimuli in the absence of alcohol or cocaine. The drug-associated stimuli were alone capable of inducing resumption of lever pressing and maintaining this behavior during repeated testing. The number of lever presses during a session represented the intensity of drug-seeking and relapse behavior. The results suggest that glutamatergic neurotransmission is involved in the modulation of drug-seeking behavior. Both alcohol and cocaine relapse were attenuated by systemic pretreatment with glutamate receptor antagonists. However, differences were found in the ability of ionotropic AMPA/kainate and NMDA receptor antagonists to regulate drug-seeking behavior. The AMPA/kainate antagonists CNQX and NBQX, and L-701,324, an antagonist with affinity for the glycine site of the NMDA receptor, attenuated cue-induced drug seeking, whereas the competitive NMDA antagonist CGP39551 and the NMDA channel blocker MK-801 were without effect. MPEP, an antagonist at metabotropic mGlu5 glutamate receptors, also decreased drug seeking, but its administration was found to lead to conditioned suppression of behavior during subsequent treatment sessions, suggesting that MPEP may have undesirable side effects. The mGluR2/3 agonist LY379268 and the mGluR8 agonist (S)-3,4-DCPG decreased both cue-induced relapse to alcohol drinking and alcohol consumption. Control experiments showed however that administration of the agonists was accompanied by motor suppression limiting their usefulness. Administration of the AMPA/kainate antagonist CNQX, the NMDA antagonist D-AP5, and the mGluR5 antagonist MPEP into the nucleus accumbens resulted also in a decrease in drug-seeking behavior, suggesting that the nucleus accumbens is at least one of the anatomical sites regulating drug seeking and mediating the effects of glutamate receptor antagonists on this behavior.

The Homeless Etiquette : Social Interaction and Behavior Among the Homeless in Taito Ward, Tokyo

The thesis focuses on the social interaction and behavior of the homeless living in Tokyo's Taito Ward. The study is based on the author's own ethnographic field research carried out in the autumn 2003. The chosen methodologies were based on the methodology called "participant observation", and they were used depending on the context. The ethnographic field research was carried out from the mid-August to the beginning of the October in 2003. The most important targets of the research were three separate loosely knit groups placed in certain parts of Taito Ward. One of these groups was based in proximity to the Ueno train station, one group gathered every morning around a homeless support organization called San'yûkai, and one was based in Tamahime Park located in the old San'ya area of Tokyo. The analysis is based on the aspects of Takie Sugiyama Lebra's theory of "social relativism". Lebra's theory consists of the following, arguably universal aspects: belongingness, empathy, dependence, place in the society, and reciprocity. In addition, all the interaction and behavior is tied to the context and the situation. According to Lebra, ritual and intimate situations produce similar action, which is socially relative. Of these, the norms of the ritual behavior are more regulated, while the intimate bahavior is less spontaneous. On the contrary, an anomic situation produces anomic behavior, which is not socially relative. Lebra's theory is critically reviewed by the author of the thesis, and the author has attempted to modify the theory to make it more adaptable to the present-day society and to the analysis. Erving Goffman's views of the social interaction and Anthony Giddens' theories about the social structures have been used as complementary thoretical basis. The aim of the thesis is to clarify, how and why the interaction and the behavior of some homeless individuals in some situations follow the aspects of Lebra's "social relativism", and on the other hand, why in some situations they do not. In the latter cases the answers can be sought from regional and individual differences, or from the inaptness of the theory to analyze the presented situation. Here, a significant factor is the major finding of the field study: the so called "homeless etiquette", which is an abstract set of norms and values that influences the social interaction and behavior of the homeless, and with which many homeless individuals presented in the study complied. The fundamental goal of the thesis is to reach profound understanding about the daily life of the homeless, whose lives were studied. The author argues that this kind of profound understanding is necessary in looking for sustainable solutions in the areas of social and housing policy to improve the position of the homeless and the qualitative functioning of the society.

The social patterning of health, smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004

The Baltic countries share public health problems typical of most Eastern European transition economies: morbidity and mortality from non-communicable diseases is higher than in Western European countries. This situation has many similarities compared to a neighbouring country, Finland during the late 1960s. There are reasons to expect that health disadvantage may be increasing among the less advantaged population groups in the Baltic countries. The evidence on social differences in health in the Baltic countries is, however, scattered to studies using different methodologies making comparisons difficult. This study aims to bridge the evidence gap by providing comparable standardized cross-sectional and time trend analyses to the social patterning of variation in health and two key health behaviours i.e. smoking and drinking in Estonia, Latvia, Lithuania and Finland in 1994-2004 representing Eastern European transition countries and a stable Western European country. The data consisted of similar cross-sectional postal surveys conducted in 1994, 1996, 1998, 2000, 2002 and 2004 on adult populations (aged 20 64 years) in Estonia (n=9049), Latvia (n=7685), Lithuania (n=11634) and Finland (n=18821) in connection with the Finbalt Health Monitor project. The main statistical method was logistic regression analysis. Perceived health was found to be worse among both men and women in the Baltic countries than in Finland. Poor health was associated with older age and lower education in all countries studied. Urbanization and marital status were not consistently related to health. The existing educational inequalities in health remained generally stable over time from 1994 to 2004. In the Baltic countries, however, improvement in perceived health was mainly found among the better educated men and women. Daily smoking was associated with young age, lower education and psychological distress in all countries. Among women smoking was also associated with urbanisation in all countries except Estonia. Among Lithuanian women, the educational gradient in smoking was weakest, and the overall prevalence of smoking increased over time. Drinking was generally associated with young age among men and women, and with education among women. Better educated women were more often frequent drinkers and less educated binge drinkers. The exception was that in Latvian men and women both frequent drinking and binge drinking were associated with low education. In conclusion, the Baltic countries are likely to resemble Western European countries rather than other transition societies. While health inequalities did not markedly change, substantial inequalities do remain, and there were indications of favourable developments mainly among the better educated. Pressures towards increasing health inequalities may therefore be visible in the future, which would be in accordance with the results on smoking and drinking in this study.

Fuel conditions and fire behavior characteristics of managed Picea abies and Pinus sylvestris forests in Finland

The objectives of this study were to analyze the impact of structural stand characteristics on ignition potential, surface fuel moisture, and fire behavior in Pinus sylvestris L. and Picea abies (L.) Karst stands in Finland and to explain stand-specific fire danger using the Canadian Fire Weather Index System and the Finnish Fire Risk Index. Additionally, the study analyzes the relationship between observed fire activity and fire weather indices at different stages of growing season. Field experiments were carried out in Pinus sylvestris or Picea abies dominated stands during fire seasons 2001 and 2002. Observations on ignition potential, fuel moisture, and fire behavior were analyzed in relation to stand structure and the outputs of the Finnish and Canadian fire weather indices. Seasonal patterns of fire activity were examined based on national fire statistics 1996 2003, effective temperature sum, and the fire weather indices. Point fire ignition potential was highest in Pinus clear-cuts and lowest in closed Picea stands. Moss-dominated surface fuels were driest in clear-cut and sapling stage stands and presented the highest moisture content under closed Picea canopy. Pinus sylvestris stands carried fire under a wide range of fire weather conditions under which Picea abies stands failed to sustain fire. In the national fire records, the daily number of reported ignitions presented its highest value during late fire season whereas the daily area burned peaked most substantially during early season. The fire weather indices correlated significantly with ignition potential and fuel moisture but were unable to explain fire behavior in the experimental fires. During the initial and final stages of the growing season, fire activity was disconnected from weather-based fire danger ratings. Information on stand structure and season stage would benefit the assessment of fire danger in Finnish forest landscape for fire suppression and controlled burning purposes.

Heterotrophic Bacteria Associated with Cyanobacteria in Recreational and Drinking Water

Cyanobacterial mass occurrences, also known as water blooms, have been associated with adverse health effects of both humans and animals. They can also be a burden to drinking water treatment facilities. Risk assessments of the blooms have generally focused on the cyanobacteria themselves and their toxins. However, heterotrophic bacteria thriving among cyanobacteria may also be responsible for many of the adverse health effects, but their role as the etiological agents of these health problems is poorly known. In addition, studies on the water purification efficiency of operating water treatment plants during cyanobacterial mass occurrences in their water sources are rare. In the present study, over 600 heterotrophic bacterial strains were isolated from natural freshwater, brackish water or from treated drinking water. The sampling sites were selected as having frequent cyanobacterial occurrences in the water bodies or in the water sources of the drinking water treatment plants. In addition, samples were taken from sites where cyanobacterial water blooms were surmised to have caused human health problems. The isolated strains represented bacteria from 57 different genera of the Gamma-, Alpha- or Betaproteobacteria, Actinobacteria, Flavobacteria, Sphingobacteria, Bacilli and Deinococci classes, based on their partial 16S rRNA sequences. Several isolates had no close relatives among previously isolated bacteria or cloned 16S rRNA genes of uncultivated bacteria. The results show that water blooms are associated with a diverse community of cultivable heterotrophic bacteria. Chosen subsets of the isolated strains were analysed for features such as their virulence gene content and possible effect on cyanobacterial growth. Of the putatively pathogenic haemolytic strains isolated in the study, the majority represented the genus Aeromonas. Therefore, the Aeromonas spp. strains isolated from water samples associated with adverse health effects were screened for the virulence gene types encoding for enterotoxins (ast, alt and act/aerA/hlyA), flagellin subunits (flaA/flaB), lipase (lip/pla/lipH3/alp-1) and elastase (ahyB) by PCR. The majority (90%) of the Aeromonas strains included one or more of the six screened Aeromonas virulence gene types. The most common gene type was act, which was present in 77% of the strains. The fla, ahyB and lip genes were present in 30 37% of the strains. The prevalence of the virulence genes implies that the Aeromonas may be a factor in some of the cyanobacterial associated health problems. Of the 183 isolated bacterial strains that were studied for possible effects on cyanobacterial growth, the majority (60%) either enhanced or inhibited growth of cyanobacteria. In most cases, they enhanced the growth, which implies mutualistic interactions. The results indicate that the heterotrophic bacteria have a role in the rise and fall of the cyanobacterial water blooms. The genetic and phenotypic characteristics and the ability to degrade cyanobacterial hepatotoxins of 13 previously isolated Betaproteobacteria strains, were also studied. The strains originated from Finnish lakes with frequent cyanobacterial occurrence. Tested strains degraded microcystins -LR and -YR and nodularin. The strains could not be assigned to any described bacterial genus or species based on their genetic or phenotypic features. On the basis of their characteristics a new genus and species Paucibacter toxinivorans was proposed for them. The water purification efficiency of the drinking water treatment processes during cyanobacterial water bloom in water source was assessed at an operating surface water treatment plant. Large phytoplankton, cyanobacterial hepatotoxins, endotoxins and cultivable heterotrophic bacteria were efficiently reduced to low concentrations, often below the detection limits. In contrast, small planktonic cells, including also possible bacterial cells, regularly passed though the water treatment. The passing cells may contribute to biofilm formation within the water distribution system, and therefore lower the obtained drinking water quality. The bacterial strains of this study offer a rich source of isolated strains for examining interactions between cyanobacteria and the heterotrophic bacteria associated with them. The degraders of cyanobacterial hepatotoxins could perhaps be utilized to assist the removal of the hepatotoxins during water treatment, whereas inhibitors of cyanobacterial growth might be useful in controlling cyanobacterial water blooms. The putative pathogenicity of the strains suggests that the health risk assessment of the cyanobacterial blooms should also cover the heterotrophic bacteria.

On the mechanical behavior of compacted pack ice : A theoretical and numerical investigation

Pack ice is an aggregate of ice floes drifting on the sea surface. The forces controlling the motion and deformation of pack ice are air and water drag forces, sea surface tilt, Coriolis force and the internal force due to the interaction between ice floes. In this thesis, the mechanical behavior of compacted pack ice is investigated using theoretical and numerical methods, focusing on the three basic material properties: compressive strength, yield curve and flow rule. A high-resolution three-category sea ice model is applied to investigate the sea ice dynamics in two small basins, the whole Gulf Riga and the inside Pärnu Bay, focusing on the calibration of the compressive strength for thin ice. These two basins are on the scales of 100 km and 20 km, respectively, with typical ice thickness of 10-30 cm. The model is found capable of capturing the main characteristics of the ice dynamics. The compressive strength is calibrated to be about 30 kPa, consistent with the values from most large-scale sea ice dynamic studies. In addition, the numerical study in Pärnu Bay suggests that the shear strength drops significantly when the ice-floe size markedly decreases. A characteristic inversion method is developed to probe the yield curve of compacted pack ice. The basis of this method is the relationship between the intersection angle of linear kinematic features (LKFs) in sea ice and the slope of the yield curve. A summary of the observed LKFs shows that they can be basically divided into three groups: intersecting leads, uniaxial opening leads and uniaxial pressure ridges. Based on the available observed angles, the yield curve is determined to be a curved diamond. Comparisons of this yield curve with those from other methods show that it possesses almost all the advantages identified by the other methods. A new constitutive law is proposed, where the yield curve is a diamond and the flow rule is a combination of the normal and co-axial flow rule. The non-normal co-axial flow rule is necessary for the Coulombic yield constraint. This constitutive law not only captures the main features of forming LKFs but also takes the advantage of avoiding overestimating divergence during shear deformation. Moreover, this study provides a method for observing the flow rule for pack ice during deformation.

Just say no? The influence of personal goals, beliefs, psychosocial adjustment, and parental relationships in drug use by adolescents

The study in its entirety focused on factors related to adolescents decisions concerning drug use. The term drug use is taken here to include the use of tobacco products, alcohol, narcotics, and other addictive substances. First, the reasons given for drug use (attributions) were investigated. Secondly, the influence of personal goals, the beliefs involved in decision making, psychosocial adjustment including body image and involvement with peers, and parental relationships on drug use were studied. Two cohorts participated in the study. In 1984, a questionnaire on reasons for drug use was administered to a sample of adolescents aged 14-16 (N=396). A further questionnaire was administered to another sample of adolescents aged 14-16 (N=488) in 1999. The results for both cohorts were analyzed in Articles I and II. In Articles III and IV further analysis was carried out on the second cohort (N=488). The research report presented here provides a synthesis of all four articles, together with material from a further analysis. In a comparison of the two cohorts it was found that the attributions for drug use had changed considerably over the intervening fifteen-year period. In relation to alcohol and narcotics use an increase was found in reasons involving inner subjective experiences, with mention of the good feeling and fun resulting from alcohol and narcotics use. In addition, the goals of alcohol consumption were increasingly perceived as drinking to get drunk, and for its own sake. The attributions for the adolescents own smoking behavior were quite different from the attributions for smoking by others. The attributions were only weakly influenced by the participants gender or by their smoking habits, either in 1984 or 1999. In relation to participants own smoking, the later questionnaire elicited more mention of inner subjective experiences involving "good feeling. In relation to the perceived reasons for other people s smoking, it elicited more responses connected with the notion of "belonging. In the second sample, the results indicated that the levels of body satisfaction among adolescent girls are lower than those among adolescent boys. Overall, dissatisfaction with one's physical appearance seemed to relate to drug use. Girls were also found to engage in more discussions than boys; this applied to (i) discussion with peers (concerning both intimate and general matters), and (ii) discussion with parents (concerning general matters). However, more than a quarter of the boys (out of the entire population) reported only low intimacy with both parents and peers. If both drinking and smoking were considered, it seemed that girls in particular who reported drinking and smoking also reported high intimacy with parents and peers. Boys who reported drinking and smoking reported only medium intimacy with parents and peers. In addition, having an intimate relationship with one's peers was associated with a greater tendency to drink purely in order to get drunk. Overall, the results seemed to suggest that drug use is connected with a close relationship with peers and (surprisingly) with a close relationship with parents. Nevertheless, there were also indications that to some extent peer relationships can also protect adolescents from smoking and alcohol use. The results, which underline the complexity of adolescent drug use, are taken up in the Discussion section. It may be that body image and/or other identity factors play a more prominent role in all drug use than has previously been acknowledged. It does appear that in the course of planning support campaigns for adolescents at risk of drug use, we should focus more closely on individuals and their inner world. More research on this field is clearly needed, and therefore some ideas for future research are also presented.