Effects of environmental enrichment on exploratory behavior, win-stay and lose-shift performance, motor sequence learning, and reversal learning during the three-lever operant task in mice.

Beneficial effects of environmental enrichment (EE) on the central nervous system have been demonstrated. Although the effects of EE on spatial learning have been extensively studied, studies on reward-based motor learning are limited. In this study we examined the effects of EE on the performance of operant tasks using three levers (A-C). Mice were divided into two groups and housed either in the control condition or in the physical EE condition. The mice were trained in three types of operant tasks in sequence. First, mice were trained to press one of the active levers for a food reward (one-lever task). Second, mice were trained to press the three levers in the order of A, B, and C (three-lever task). Third, the lever order was reversed to C, B, and A (reverse three-lever task). We found some behavioral differences between control and EE mice. When all three levers were active in the one-lever task, mice tended to press the three levers equally at first, then shifted to press one lever preferentially. This behavioral shift from exploration to exploitation was delayed in EE mice. When only one lever was active, EE mice showed a higher lose-shift performance. In the three-lever and reverse three-lever tasks, EE mice pressed three levers more often and acquired more food rewards, compared to control mice, although the success rate in both tasks was not different between the two groups. These behavioral features observed in EE mice (higher lose-shift performance and higher trial and error activity) might be advantageous when circumstances are not stable.

A dominant-negative FGF1 mutant (the R50E mutant) suppresses tumorigenesis and angiogenesis.

Fibroblast growth factor-1 (FGF1) and FGF2 play a critical role in angiogenesis, a formation of new blood vessels from existing blood vessels. Integrins are critically involved in FGF signaling through crosstalk. We previously reported that FGF1 directly binds to integrin αvß3 and induces FGF receptor-1 (FGFR1)-FGF1-integrin αvß3 ternary complex. We previously generated an integrin binding defective FGF1 mutant (Arg-50 to Glu, R50E). R50E is defective in inducing ternary complex formation, cell proliferation, and cell migration, and suppresses FGF signaling induced by WT FGF1 (a dominant-negative effect) in vitro. These findings suggest that FGFR and αvß3 crosstalk through direct integrin binding to FGF, and that R50E acts as an antagonist to FGFR. We studied if R50E suppresses tumorigenesis and angiogenesis. Here we describe that R50E suppressed tumor growth in vivo while WT FGF1 enhanced it using cancer cells that stably express WT FGF1 or R50E. Since R50E did not affect proliferation of cancer cells in vitro, we hypothesized that R50E suppressed tumorigenesis indirectly through suppressing angiogenesis. We thus studied the effect of R50E on angiogenesis in several angiogenesis models. We found that excess R50E suppressed FGF1-induced migration and tube formation of endothelial cells, FGF1-induced angiogenesis in matrigel plug assays, and the outgrowth of cells in aorta ring assays. Excess R50E suppressed FGF1-induced angiogenesis in chick embryo chorioallantoic membrane (CAM) assays. Interestingly, excess R50E suppressed FGF2-induced angiogenesis in CAM assays as well, suggesting that R50E may uniquely suppress signaling from other members of the FGF family. Taken together, our results suggest that R50E suppresses angiogenesis induced by FGF1 or FGF2, and thereby indirectly suppresses tumorigenesis, in addition to its possible direct effect on tumor cell proliferation in vivo. We propose that R50E has potential as an anti-cancer and anti-angiogenesis therapeutic agent ("FGF1 decoy").

[Evaluation of educational effects on drug dependence abstinence for convicts].

The object of this study is to evaluate the educational effects of group work sessions on drug dependence abstinence for convicts in Fukui Prison. Questionnaire surveys were conducted among participants on the first and last session. The results of surveys were analyzed quantitatively. The average ages of 50 respondents were 39 years. 95.9% of them used methamphetamine among drugs and the majority has used drugs for the past 5 years. 93.9% of respondents had no medical treatment histories and 95.8% of them have not used any formal consultations. The survey result before the sessions showed that 75.5% of respondents showed positive stances towards participations on educational group work sessions. The survey after the sessions showed 67.4% of respondents were able to talk their drug problems in group meetings and 87.0% responded that group work sessions were helpful for solving drug problems. Also, 80.0% responded that they can stop using drugs and the percentage dropped by 11.0% from the first session. In terms of the participation in self-help groups after releases from the prison, the majority responded negatively, although 78.0% showed positive responses to using consultation services. The outcomes by means of evaluation scale also showed a significant improvement on denial and no relevant change on interpersonal trusts. This study revealed that it was possible to confirm the effectiveness of drug abstinence education through group work. It is important to consider three points in further studies; 1) cooperation between judicial and medical institutions for introducing consultation and medical treatments among convicts; 2) follow-up programs for reinforcing education on drug abstinence; 3) social welfare services in cooperation with educational effects to prevent repeated offences.

Mental health and emotional relationships of family members whose relatives have drug problems.

The presence of a drug abuser in a family can seriously affect the family's mental health and relationships. This study focuses on the stress of families of drug abusers, relationships, and their relevant factors, as well as examines ways to support them. The subjects of this study were family members of drug abusers treated at drug abuser family support groups, medical institutions, or municipal mental health and welfare centers. To these institutions, 1,298 questionnaires were sent, and 543 responses with sufficient data were used for analysis. The survey consisted of the 12-item General Health Questionnaire (GHQ-12), and questionnaire items regarding disruptions to family life, relationship with drug users, and the use of family support services. The survey results showed that the mean GHQ score was 4.5, and those whose score are cut-off 3 and more, indicating poor mental health accounted for 54.7%. More than half of the subjects responded that drug problems have affected family members in terms of the health condition, daily living, and financial problems. Regarding emotional relationships with the addicts, most of the families answered that they have had negative feelings toward them, such as "being dragged into drug problems" and "being over-protective". A significant correlation was observed between the GHQ score and family members' relationship with the addict, and these variables were closely correlated with participation in the family group, the status of drug abstinence, living environment, and participation in a self-support group by the addict. As the results, most of the family members of drug users have problems with mental health and the recovery of relationships even though they have accessed support centers, and it was verified that the family support group works effectively to help solve their problems.

[Study on support group for families with drug problems--aims of support and examination of group participators' situation].

This study examined the states of former Freedom family groups and DARC family group and analyzed their correlation with helping purposes. The two groups showed many common points. However, in DARC family groups, our data showed that the average of the ages of family members and drug addicts were higher and that they participated in their group for a longer period. Our other findings were followings; 1) Recovery of family members: this research evaluated the recovery of family members measuring following questions on drug problems: family function, co-dependency and self-esteem. As for cognition on drug problems, there were no significant differences between two groups. In contrast, the family function of Freedom was superior to that of DARC. These findings imply that, considering short periods of their participation in the group, Freedom family group has good effect on recovery of family. 2) Linking with recovering facility (DARC): participation rate of addicts of DARC family group to DARC was high. Therefore, the DARC family group has good performance on helping purposes. 3) Introduction to Nar-Anon: the high rate of participation in Nar-Anon of members in Freedom family groups and their longer period of participation were showed with positive statistical significant. This means also good effect on helping process. 4) Recovery of addicts: regarding medical treatments, circumstances of drug abuse and the employment rate, there were no significant differences between two groups. Differences were viewed in relation to the participation rate of concerned person of DARC family group in DARC and NA, period of abstinence and forms of dwelling. The period of participation in groups presented differences and in relation to recovery of addicts the level of addicts differences were clear.

[Practice and evaluation of group work programs for families with drug dependent people].

This study aims at examining the evaluation of a group work program for families with drug dependent people which has started at a Non-Profit Organization, Freedom in Osaka from 2004. The aims of the group work program included 1) provision of knowledge and information regarding drug dependency and recovery; 2) support for families influenced by drug related problems; 3) support for coping properly with drug dependents; 4) support for recovery of family relationship; 5) introduction to self-help groups (Nar-Anon). Two questionnaire surveys were conducted in 2005 and 2006 among the participants of the group work program to evaluate the effects of the program. In 2005, a questionnaire survey was conducted for 98 newcomers to a group work program for drug dependent people and their families and had 64 responses. The survey in 2006 revealed that mother's family functions were low and addictive tendencies of mothers and wives were high. In 2006 a follow-up survey was conducted among the respondents of the 2005 survey and obtained 36 responses. The average numbers of participation among these respondents were 5.4. The survey in 2006 revealed that the numbers of participation to the program were related correlatively to the improvement of family functions and the decrease of addictive tendencies of mothers and wives. In addition, 31% of the drug dependents stayed sober and 12% responded "the drug use is same as a year ago", or "the use has increased". It will be predicted that the improvement of family functions and the recovery of family relationship decreased the drug use of the dependents as an effect of the group work program.

[Comparative studies on patient's and family's basic attributes, psychosocial states and treatment prognoses at three medical institutions for treatment of alcoholism].

A research by questionnaire was conducted at three medical institutions, on basic attributes and psychosocial states of alcoholics' as first time inpatient and respective families. After a year of research, additional study was conducted in regard of abstinence, treatment continuation as outpatient, participation in self-help groups, and family's participation in family groups. Outcomes of researches' statistical analyses showed significant differences concerning medical institutions and basic attributes for the items: treatment histories of alcoholism, treatment or inpatient in other medical departments and alcoholic's family history,; but these differences were considered to be associated with varied courses of referrals. In relation to medical institutions with patients and family's psychosocial states, there were no significant differences on the outcomes of five scales. As for the correlation between medical institutions with a year's prognoses there were no significant differences concerning abstinence and treatment continuation as outpatient. In case of participation in self-help groups and family groups, the prognoses showed significant differences but these differences were considered to be related to varied treatments and different helping ways of medical institutions and varied conditions of local communities for mentioned helps.

[Research on the basic attributes and psychosocial factors of alcoholics and their families in relation with prognosis after a year of treatment].

Outcomes of a survey by questionnaire on 265 male alcoholics and their 230 families relating basic attributes, psychosocial factors and its correlation with prognosis after a year of inpatient treatment were examined. As for the basic attributes, factors such as family bond, referral for treatment by specialists and the treatment history were correlated with good prognosis . In regard to psychosocial factors, "cohesion" and high level of family function, "denial", family's "obsessive-compulsive traits" were related to positive prognosis. However contrary to preceding studies, "adaptability", "self-acceptance" and "domination trend" were also correlated to good prognosis. In the beginning of treatment, rigid family function were indicated by "adaptability", "domination trend" and "hitting the bottom" occasioned by "self-acceptance", evidenced to be positively correlated to prognosis after a year.

[Research on factors for dropout from treatment by outpatients of alcohol abuse or alcohol dependence (I)--Based on statements of medical treatment personnel].

This study have in view the elucidation of factors related to treatment dropouts of alcohol abuse and dependence outpatients. The medical staff of the clinic "S" held two workshops and the discussion data was analyzed by a Total Quality Management (TQM) method to see a strategy for avoiding dropout. There were three side characteristics, for dropout factors, i.e., patients' and clinic's and relations between two sides. To cope with patients' factors a better communication with patients by medical staff was suggested. For clinic "S", suggestions was given to improve treatment environment such as consultation and treatment systems and better relationship with patients.

[Research on factors for dropout from treatment by outpatients of alcohol abuse or alcohol dependence (II)--Based on questionnaire's outcome].

This research examines a strategy to avoid dropout from treatment by outpatients of alcohol abuse and dependence. Questionnaire was used and outcome was analyzed in order to elucidate factors of dropout and examine measures for its avoidance. The questionnaire made on the occasion of "Research on Factors of Dropout from Treatment by Outpatients of Alcohol Abuse or Dependence (I)" was used. 376 subjects was surveyed with 178 answers (47.3%), out of which 167 (44.5%) were valid. The analyses of answers showed as factors of dropout: dissatisfaction for content and environment of treatment, transfer to internal medicine department, and almost every day drinking. Reasons for continuation of treatment were: satisfaction for content of medical examination, admission to specialized treatment facilities, participation to self-help groups, feeling of happiness for treatment, since beginning intended to continue treatment. As a measure to avoid treatment dropout, improvements of content and environment of treatment and better relationship among medical staffs and clients were suggested.