Attitude of patients with mood disorder toward clinical trials in Japan.
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Biomedical subjects
Publications and source records attributed to Toshihide Kuroki.
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Stimulation of dopamine receptors may induce striatal Homer 1a, an immediate-early gene (IEG) that is involved in the molecular mechanism for the signaling pathway of the group I metabotropic glutamate receptors. This study examined the effects of the agonists for dopamine D(1)-like and D(2)-like receptors on gene expression of Homer 1a, in comparison with the IEG c-fos expression, in the discrete brain regions of rats. The D(1)-like agonist SKF38393 (20 mg/kg, s.c.) significantly increased the mRNA levels of Homer 1a in the striatum and nucleus accumbens, but not in the medial prefrontal cortex or hippocampus, 2 h after injection, whereas the D(2)-like agonist quinpirole (1 mg/kg, s.c.) had no significant effect on Homer 1a mRNA levels in any brain region examined. Co-administration of SKF38393 and quinpirole significantly increased Homer 1a mRNA levels in the striatum, nucleus accumbens and hippocampus, while this effect was not significantly greater than that of SKF38393 alone. Any treatment did not affect the mRNA levels of other splicing variants, Homer 1b or 1c. In contrast, combination of both dopamine agonists produced a greater increase than SKF38393 did in the mRNA levels of c-fos in the nucleus accumbens, striatum and substantia nigra. These results suggest that stimulation of D(1)-like receptors, but not D(2)-like receptors, may induce gene expression of Homer 1a in the striatum and nucleus accumbens. However, in contrast to c-fos expression, it is unlikely that co-activation of both D(1)-like and D(2)-like receptors exerts a synergic action on Homer 1a expression in these regions.
In aged rats, although learning and memory impairment is prominent, both the number of granular cells and the degree of neuronal progenitor proliferation in the hippocampus are known to be preserved. We examined the association between the survival of newly generated neurons in the hippocampus and the learning ability in aged rats. By using BrdU, a cell proliferation marker to determine neurogenesis and contextual fear conditioning to determine learning ability, we found that in aged rats, along with memory impairment, the survival of both the proliferated cells at baseline and those enhanced by contextual fear conditioning decreased remarkably. These results suggest that the integration of newly generated neurons into hippocampal circuitry is decreased with aging, this phenomenon may, in part, explain the decline in learning and memory in aged rats.
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Taijin Kyofusho (TKS), a disorder characterized by a fear of interpersonal relations, and regarded as a culture-bound disorder in Japan, is related to social anxiety disorder (SAD). A variant of TKS, the 'offensive type' involves fear of offending others by one's inappropriate social behavior or appearance. Reports of offensive-type TKS have hitherto been limited to a small number of case reports. To delineate the characteristics of offensive-type TKS and to determine the patterns of fear and factors involved, we investigated 111 Japanese university students who reported feeling tense or nervous in social or interpersonal interactions. We analyzed subjects' responses to items on a scale for TKS, and isolated five factors. Cluster analysis of the factor scores revealed a group (N = 25) with symptomatic profiles that fit 'offensive-type TKS.' Despite this group's high TKS scores, their scores on the Liebowitz Social Anxiety Scale-Japanese version were relatively low. Our results suggest that the symptoms of some TKS sufferers do not fall within the SAD spectrum.
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New atypical antipsychotic drugs such as risperidone, olanzapine and quetiapine, that have been modeled on the prototype agent clozapine and developed since the 1990's, are now referred to as second-generation antipsychotics (SGA). It has been proposed by Meltzer (1989) that the interaction between serotonin (5-HT) and dopamine (DA) systems may play a critical role in the mechanism of action for atypical antipsychotics because potent 5-HT2A receptor antagonism together with relatively weak D2 receptor antagonism could differentiate most atypical antipsychotics from typical antipsychotics. This serotonin-dopamine hypothesis has become a useful model for studying and developing new drugs to achieve a significant antipsychotic effect with lower incidence of extrapyramidal side effects compared to first-generation antipsychotics. In contrast, Kapur and Seeman (2001) argued the alternative "fast-off" theory that clozapine occupies D2 receptors to a similar extent as typical antipsychotics do and then rapidly dissociates from D2 receptors. This paper reviews the current issues on the serotonin-dopamine hypothesis and recent research on the role of 5-HT receptor subtypes in the mechanism of action for SGA. In particular, SGA-induced DA release in the prefrontal cortex, possibly through the functional activation of 5-HT1A receptors by 5-HT2A and D2 receptor-mediated interaction, may be the basis for the cognitive effects of SGA.
(+/-)-([1-(2,5-Dimethoxy-4-iodophenyl)-aminopropane]-hydrochloride) (DOI) (2.5 mg/kg), a 5-HT(2A/2C) agonist, significantly potentiated D-amphetamine (AMPH) (1 mg/kg)-induced dopamine (DA) release in rat medial prefrontal cortex (mPFC) and nucleus accumbens (NAC). This effect of DOI was completely prevented by M100907 (1 mg/kg), a selective 5-HT(2A) antagonist, which by itself had no effect on basal and AMPH-induced DA release in either region. Thus, 5-HT(2A) receptor agonism potentiates AMPH-induced DA release in the mPFC and NAC.
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Because of the possible interaction between adenosine receptors and dopaminergic functions, the compound acting on the specific adenosine receptor subtype may be a candidate for novel antipsychotic drugs. To elucidate the antipsychotic potential of the selective adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA), we examined herein the effects of CPA on phencyclidine (PCP)-induced behavior and expression of the immediate-early genes (IEGs), arc, c-fos and jun B, in the discrete brain regions of rats. PCP (7.5 mg/kg, s.c.) increased locomotor activity and head weaving in rats and this effect was significantly attenuated by pretreatment with CPA (0.5 mg/kg, s.c.). PCP increased the mRNA levels of c-fos and jun B in the medial prefrontal cortex, nucleus accumbens and posterior cingulate cortex, while leaving the striatum and hippocampus unaffected. CPA pretreatment significantly attenuated the PCP-induced increase in c-fos mRNA levels in the medial prefrontal cortex and nucleus accumbens. CPA also significantly attenuated the PCP-induced arc expression in the medial prefrontal cortex and posterior cingulate cortex. When administered alone, CPA decreased the mRNA levels of all IEGs examined in the nucleus accumbens, but not in other brain regions. Based on the ability of CPA to inhibit PCP-induced hyperlocomotion and its interaction with neural systems in the medial prefrontal cortex, posterior cingulate cortex and nucleus accumbens, the present results provide further evidence for a significant antipsychotic effect of the adenosine A(1) receptor agonist.
BACKGROUND: Patients who frequently change physicians without letters of referral are common, and this has become a source of concern among primary care doctors in Japan. Previous studies have shown a correlation between psychiatric disorders and patient dissatisfaction and the utilization of medical resources. Abnormal illness behaviours such as hypochondria and inappropriate treatment seeking have been associated with various psychiatric disorders. The relationship between illness behaviour and self-referral in Japan has yet to be fully explored. OBJECTIVES: Our aim was to describe the characteristic illness behaviour and satisfaction level of self-referred patients in the general medicine clinic of Saga Medical School Hospital. METHODS: Using the Japanese version of the Illness Behaviour Questionnaire (J-IBQ), we examined the illness behaviour of 277 self-referred patients visiting the clinic. Patient satisfaction with previous medical care was examined with the use of our original Patient Satisfaction Questionnaire. The results were compared with those for physician-referred patients. RESULTS: Self-referred patients differed significantly from original-visit patients on the GH (general hypochondriasis), DC (disease conviction), AD (affect disturbance) and I (irritability) scales and from physician-referred patients on the GH and DC scales. In comparison with physician-referred patients, self-referred patients showed significant dissatisfaction with their most recent medical visit elsewhere. Dissatisfaction toward the medical staff, especially the doctors, was stronger than that toward the medical environment, waiting time or the on-site medical equipment. CONCLUSIONS: It is important to give patients appropriate overall support, not only physical but also emotional, when they first visit a general physician for medical advice. The J-IBQ may be a useful instrument for primary identification of self-referral patients with probable somatization syndromes. Open doctor-doctor and patient-doctor communication is necessary to increase patient satisfaction, which may be helpful to minimize the self-referral phenomenon in Japan.