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.

Long-term Outcome of DSM-IV Major Depressive Disorder in Psychiatric Care

Much of what we know regarding the long-term course and outcome of major depressive disorder (MDD) is based on studies of mostly inpatient tertiary level cohorts and samples predating the era of the current antidepressants and the use of maintenance therapies. In addition, there is a lack of studies investigating the comprehensive significance of comorbid axis I and II disorders on the outcome of MDD. The present study forms a part of the Vantaa Depression Study (VDS), a regionally representative prospective and naturalistic cohort study of 269 secondary-level care psychiatric out- and inpatients (aged 20-59) with a new episode of DSM-IV MDD, and followed-up up to five years (n=182) with a life-chart and semistructured interviews. The aim was to investigate the long-term outcome of MDD and risk factors for poor recovery, recurrences, suicidal attempts and diagnostic switch to bipolar disorder, and the association of a family history of different psychiatric disorders on the outcome. The effects of comorbid disorders together with various other predictors from different domains on the outcome were comprehensively investigated. According to this study, the long-term outcome of MDD appears to be more variable when its outcome is investigated among modern, community-treated, secondary-care outpatients compared to previous mostly inpatient studies. MDD was also highly recurrent in these settings, but the recurrent episodes seemed shorter, and the outcome was unlikely to be uniformly chronic. Higher severity of MDD predicted significantly the number of recurrences and longer time spent ill. In addition, longer episode duration, comorbid dysthymic disorder, cluster C personality disorders and social phobia predicted a worse outcome. The incidence rate of suicide attempts varied robustly de¬pending on the level of depression, being 21-fold during major depressive episodes (MDEs), and 4-fold during partial remission compared to periods of full remission. Although a history of previous attempts and poor social support also indicated risk, time spent depressed was the central factor determining overall long-term risk. Switch to bipolar disorder occurred mainly to type II, earlier to type I, and more gradually over time to type II. Higher severity of MDD, comorbid social phobia, obsessive compulsive disorder, and cluster B personality disorder features predicted the diagnostic switch. The majority of patients were also likely to have positive family histories not exclusively of mood, but also of other mental disorders. Having a positive family history of severe mental disorders was likely to be clinically associated with a significantly more adverse outcome.

Customer Energy in Relationships

All companies have a portfolio of customer relationships. From a managerial standpoint the value of these customer relationships is a key issue. The aim of the paper is to introduce a conceptual framework for customers’ energy towards a service provider. Customer energy is defined as the cognitive, affective and behavioural effort a customer puts into the purchase of an offering. It is based on two dimensions: life theme involvement and relationship commitment. Data from a survey study of 425 customers of an online gambling site was combined with data about their individual purchases and activity. Analysis showed that involvement and commitment influence both customer behaviour and attitudes. Customer involvement was found to be strongly related to overall spending within a consumption area, whereas relationship commitment is a better predictor of the amount of money spent at a particular company. Dividing the customers into four different involvement / commitment segments revealed differences in churn rates, word-of-mouth, brand attitude, switching propensity and the use of the service for socializing. The framework provides a tool for customer management by revealing differences in fundamental drivers of customer behaviour resulting in completely new customer portfolios. Knowledge of customer energy allows companies to manage their communication and offering development better and provides insight into the risk of losing a customer.

Elämänmuutoksen, jännityksen ja asiantuntijuuden representointi Veikkaus Oy:n mainonnassa vuosina 1970— 2006

Aim of this master's thesis paper for consumer economics, is to research gambling advertisements in Finland over a period of 35 years, from 1970 to 2006. Veikkaus Oy (later Veikkaus), was founded in 1940, as one of the three licensed gambling organizations in Finland. Material for the current research comprised 1494 advertisements published by Veikkaus in newspapers and magazines at that time. Veikkaus has the exclusive licence to organize lotto games, sport games, instant games and other draw games in Finland. The other two operators, The Finnish Slot Machine Association RAY and Fintoto (on-track horse betting), were not included in the current analysis. This study has been completed according to research contract and grand by the Finnish Foundation for Gaming Research (Pelitoiminnan tutkimussäätiö). In general, advertisements reflect surrounding culture and time, and their message is built on stratified meanings, symbols and codes. Advertising draws the viewer's attention, introduces the advertised subject, and finally, affects the individual's consumption habits. However, advertisements not only work on individual level, but also influence public perception of the advertised product. Firstly, in order to assess gambling as a phenomenon, this paper discusses gambling as consumer behaviour, and also reviews history of gambling in Finland. Winning is a major feature of gambling, and dreaming about positive change of life is a centre of most gambling ads. However, perceived excitement through risk of losing can also be featured in gambling ads. Secondly, this study utilizes Veikkaus’ large advertising archives, were advertising data is analyzed by content analysis and the semiotic analysis. Two methods have been employed to support analyzing outcome in a synergistic way. Content analysis helps to achieve accuracy and comprehensiveness. Semiotic analysis allows deeper and more sensitive analysis to emerged findings and occurrences. It is important to understand the advertised product, as advertising is bound to the culture and time. Hence, to analyze advertising, it is important to understand the environment where the ads appear. Content analysis of Veikkaus data discovered the main gambling and principal advertisement style for each.period. Interestingly, nearly half of Veikkaus’ advertisements promoted topic other than “just winning the bet”. Games of change, like Lotto, typically advertised indirectly represented dreams about winning. In the category of skill gambling, features were represented as investment, and the excitement of sporting expertise was emphasized. In addition, there were a number of gambling ads that emphasize social responsibility of Veikkaus as a government guided organization. Semiotic methods were employed to further elaborate on findings of content analysis. Dreaming in the advertisements was represented by the product of symbols, (e.g. cars and homes) that were found to have significance connection with each other. Thus, advertising represents change of life obtained by the winning. Interestingly, gambling ads promoting jackpots were often representing religious symbolisms. Ads promoting social responsibility were found to be the most common during economical depression of the 90’s. Deeper analysis showed that at that time, advertisements frequently represented depression-related meanings, such as unemployment and bank loans. Skill gaming ads were often represented by sports expertise – late 90’s, their number started sky rocketing, and continued increasing until 2006 (when this study ended). One may conclude that sport betting draws its meanings from the relevant consumer culture, and from the rules and features of the betted sport.