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Volume 119 (2002)
- Issue 6 Pages 319-
- Issue 5 Pages 273-
- Issue 4 Pages 201-
- Issue 3 Pages 135-
- Issue 2 Pages 65-
- Issue 1 Pages 7-
Volume 119, Issue 6
Displaying 1-4 of 4 articles from this issue
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Review
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Yoshihisa KITAMURA, Hiroaki ARAKI, Yutaka GOMITAArticle type: Review
2002 Volume 119 Issue 6 Pages 319-325
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSPsychoendocrinology studies of depressed patients focus on the disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Abnormalities in the HPA axis have been noted in depressed patients. Numerous data have demonstrated the existence of reciprocal interactions between the central serotonin (5-HT) system and HPA axis. These interactions are of particular relevance when considering pathological conditions, such as depression, in which modifications of both the 5-HT system and HPA axis have been evidenced. In our laboratory, we examined the effects of adrenocorticotropic hormone (ACTH) on the immobilization of rats in the forced swim test and on the wet-dog shakes induced by the DOI, 5-HT2 receptor agonist with the administration of imipramine and lithium. The reduction of immobility, induced by the chronic administration of imipramine for 15 days, was blocked by treatment with ACTH for 14 days. And, chronic ACTH treatment for 14 days increased the wet-dog shake response. This effect of ACTH was not inhibited by a 14-day administration of imipramine. Accordingly, the chronic treatment of rats with ACTH may prove to be an effective model for antidepressant-treatment-resistant depression. We believe that behavioral pharmacological and molecular biological research into the interaction between the 5-HT and HPA axis will elucidate the pathogenesis of depression or antidepressant-treatment-resistant depression and the mechanism of antidepressants action.
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Thesis
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Yoshiaki MIYAMOTO, Toshitaka NABESHIMAArticle type: Thesis
2002 Volume 119 Issue 6 Pages 327-335
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSThe NMDA subtype of glutamate receptor (GluR) plays an important role in excitatory neurotransmission, synaptic plasticity, brain development, and neurodegeneration. NMDA receptors are inherent high Ca2+-permeable channels, which are formed by heteromeric assembly of the GluRζ1 subunit (NR1) and any one of four GluRε subunits (GluRε1-4; NR2A-D). Mice lacking the GluRε1 subunit exhibited a malfunction of NMDA receptors, as evidenced by reduction of NMDA receptor channel current, hippocampal long-term potentiation, [3H]MK-801 binding, and NMDA-stimulated 45Ca2+ uptake. A biochemical analysis revealed a hyperfunction of dopaminergic and serotonergic neuronal systems in the frontal cortex and striatum of GluRε1 mutant mice. The enhancement of dopaminergic neuronal activity in the striatum, at least, due to the disinhibition of inhibitory GABAergic neuronal input. GluRε1 mutant mice showed an increase of locomotor activity in a novel environment attributed to the hyperfunction of the dopaminergic neuronal system, and an impairment of spatial, contextual, and latent learning. These findings provide evidence that NMDA receptors regulate behavior through the modulation of not only glutamatergic but also GABAergic and dopaminergic neuronal systems. Moreover, it is suggested that GluRε1 mutant mice are useful as an animal model, which is associated with the malfunction of NMDA receptors and hyperfunction of the dopaminergic neuronal system.
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Technical Note
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Tsukasa OKIYONEDA, Hirofumi KAIArticle type: Technical Note
2002 Volume 119 Issue 6 Pages 337-344
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSDNA transfection techniques are necessary to perform the high throughput screening (HTS) for drug discovery. Among many transfection techniques, we will recommend the adenovirus vector for HTS as a particularly useful method. The adenovirus vector has attracted a great deal of attention as a vector for gene therapy and is also useful for studying gene functions in differentiated cells such as neurons and muscle cells. An efficient method of constructing recombinant adenoviruses has been established. In this article, we will introduce the method to produce the desired recombinant adenoviruses and show our findings using these adenoviruses.
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Motohiko CHACHIN, Yoshihisa KURACHIArticle type: Technical Note
2002 Volume 119 Issue 6 Pages 345-351
Published: 2002
Released on J-STAGE: January 21, 2003
JOURNAL FREE ACCESSRecently, there has been considerable attention focused on drugs that prolong the QT interval of the electrocardiogram. This occasionally evolves to fetal, polymorphic ventricular arrhythmias, torsades de pointes. Therefore, the early detection of the risk of drug-induced QT prolongation is important for avoiding the adverse cardiovascular effect in clinical use. It has been suggested that the QT prolongation and ventricular arrhythmia caused by drugs might be secondary to their ability to interfere with cardiac potassium channels involved in action potential repolarization and in particular with rapidly activating delayed rectifier K+ current (IKr). In cardiac myocytes, IKr contributes to termination of the plateau phase of action potential. The ether-a-go-go related gene in humans expressed a K+ channel current with biophysical characteristics similar to those of IKr. Electrophysiological studies on cloned HERG channels can provide fundamental information concerning the cardiac safety profile of new developing drugs.
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