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Volume 115, Issue 1
Displaying 1-7 of 7 articles from this issue
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Masahiro IMAIZUMI, Kenji ONODERA2000 Volume 115 Issue 1 Pages 5-12
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSMany animal models of anxiety have been reported;for example, Geller-type or Vogel-type anticonflict tests and ethologically based tests without punishment such as a light dark test, ahole-board test, a socialinteraction test, an elevated plus-maze test and so on.These models were pharmacologically validated by the evidence that clinically useful anxiolytic benzodiazepines were active, but activities of serotonergic anxiolytics in these models were inconsistent. These models might measure a mixture of several types of anxiety.Many disorders of anxiety are classified in the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) and several disorders can not be treated with benzodiazepines very well.Animal models to evaluate the drugs for the benzodiazepine-untreatable disorders are needed.Graeffetal.performed studies to measure inhibitory avoidance latency from an enclosed arm to open arms and escape latency from the open arms to theenclosed arm as parameters of conditioned and unconditioned fears, respectively, in the elevated T-maze inrats.The latter was suggested for use in the evaluation of drugs effi-cacious on a panic disorder.Amarble burying test as an animal model for an obsessive-compulsive disor-der was also reported.However, establishment of the models for these disorders remains for future investigations.View full abstractDownload PDF (550K) -
Taeko HATA, Eiji ITOH, Hiroyuki NISHIKAWA2000 Volume 115 Issue 1 Pages 13-20
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSAnxiety observed in animals subjected to stress was stated in relation to anxiety level and biological backgrounds of animals, changes in neurotransmitters and causal stressors. (1)Anxiety is thought to be a negative emotion caused by many kinds of stress such as restraint stress, SART (specific alternation of rhythm in temperature) stress (a repeated cold stress caused by environmental temperature), social stress, etc. (2)Emotional behavior in those stressed animals were attenuated by anxiolytics like diazepam, a benzodiazepine receptor agonist and buspirone, a serotonin (5-HT) 1A agonist. (3)Stressed rats had changed brain levels of a variety of neurotransmitters such as corticotropin-releasing factor (CRF), noradrenaline, 5-HT, dopamine, acetylcholine, histamine, cholecystokinin, etc. The percentage of time spent on the open arms of an elevated plus-maze apparatus decreased in those stressed animals. Abnormal elevated plus-maze behaviors were attenuated by diazepam, buspiron and a CRF antagonist. (4)Anxiety level differs according to the coping strategy of the recipients. Rats of different strain, sex, aging and or family display different behaviors in elevated plus-maze. (5)Stress-induced anxiety-related behaviors were observed when levels of some neurotransmitters became unbalanced. Thus modulators of unbalanced brain substances are thought to have anxiolytic properties.View full abstractDownload PDF (674K) -
Kazuo TORIIZUKA, Maho MIZOWAKI, Toshihiko HANAWA2000 Volume 115 Issue 1 Pages 21-28
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSIn the menopause transition, around 35 % of women will seek medical help for menopausal symptoms. At the climacteric, various symptoms such as forgetfulness, anxiety, depressive neurosis, abnormal sensation, hot flush and sleeplessness are often observed due to hypofunction of the ovaries. There is some indication that women become more anxious during times of relatively low level of estrogen and progesterone such as premenstrual syndrome, premenstrual dysphoric disorder, maternity blues and menopausal state. The exact mechanism behind it is still unclear but is probably related to the decrease of ovarian hormones, which may be triggering psychiatric mood disorders. It is known that ovarian hormones act on specific areas of the brain and apper to act as anxiolytics. Certain progesterone metabolites are anesthetic and have anti-epileptic and anxiolytic properties. These steroids modulate the type A gamma-aminobutyric acid (GABAA) benzodiazepine receptor. This may help explain the increased frequency of anxiety disorders and mood disorders in the early postmenopausal period. In addition, estrogen also improves memory and performance in patients with mild Alzheimer's dementia. These effects can be related to amplifying effects of estrogen on excitatory amino acids in the brain. This is suggested that gonadal steroidal hormones seemed to be one of the essential substances for the maintenance of the limbic system and forebrain function which regulated anxiety, mood, memory and cognitive functions in menopausal women.View full abstractDownload PDF (664K) -
Minoru TSUJI, Hiroshi TAKEDA, Teruhiko MATSUMIYA2000 Volume 115 Issue 1 Pages 29-38
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSIt has been recently suggested that the central serotonin (5-HT) nervous system may be involved in the modulation of anxiety. Especially, the possible importance of 5-HT1A receptors in anxiety was raised by evidence that the anxiolytic properties of 5-HT1A-receptor agonists have now been confirmed in clinical studies. On the other hand, in preclinical studies using various animal models of anxiety, these novel agents tend to have weak and/or variable effects in some paradigms used to detect the anxiolytic activities of benzodiazepines. These differential patterns of drug effects within various models promote the concept of “multiplicity of anxiety”. Recently, a new experimental model called the T-maze was developed in attempts to analyze a different type of anxiety; i.e., conditioned fear and unconditioned fear response. The results of a series of behavioral studies using the T-maze test suggest that distinct 5-HT pathways may modulate the different classes of anxiety. In our recent studies using the hole-board test, apparent differential behavioral effects between benzodiazepine anxiolytics and 5-HT1A agonists on emotionality of stressed mice were also observed. These results suggest that benzodiazepine or 5-HT1A receptors may play a different role in modulating emotionality. These studies may provide new information to investigate the pathophysiological characteristics of various types of anxiety disorders and to develop novel therapeutic agents.View full abstractDownload PDF (772K) -
Machiko MATSUMOTO, Mitsuhiro YOSHIOKA2000 Volume 115 Issue 1 Pages 39-44
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSAn overview of the behavioral, electrophysiological and neurochemical data found in the literature concerning the involvement of serotonin (5-HT) receptors in the regulation of anxiety was presented on the basis of animal models. At present, 5-HT receptors are classified into 7 families including at least 14 subtypes. Among these 5-HT receptors, it is conceivable that 5-HT1A-receptor-mediated effects are the most important part of the mechanism of anxiety. The demonstrated efficacy of 5-HT1A-receptor partial agonists in anxiety disorders has emphasized the importance of these receptors. Enhanced anxiety was observed in mutant mice lacking 5-HT1A receptors. In 5-HT1B receptors knockout mice, on the other hand, aggressive behavior was increased. Some of the selective antagonists acting on 5-HT2 and 5-HT3 receptors have shown the anxiolytic effects in various animal models. Inactivation of mRNA encoding 5-HT6 receptors using antisense oligonucleotide produced decreases in cortical 5-HT release enhanced by anxiety. These observations lead to the suggestion that different mechanisms, mediated by various 5-HT receptors, are involved in the pathogenesis of anxiety.View full abstractDownload PDF (548K) -
Hiroo OGURA, Takashi KOSASA, Shin ARAKI, Yoshiharu YAMANISHI2000 Volume 115 Issue 1 Pages 45-51
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSOne of the most consistent changes associated with Alzheimer's disease (AD) is a deficit in central cholinergic neurotransmission. Donepezil hydrochloride (DPZ), a novel class of cholinesterase (ChE) inhibitors, inhibits degradation of acetylcholine (ACh) and activates central cholinergic system. In in vitro studies, DPZ more selectively inhibited acetylcholinesterase (IC50: 6.7 nM) than butyrylcholinesterase (IC50: 7400 nM), while tacrine inhibited both acetylcholinesterase (IC50: 77 nM) and butyrylcholinesterase (IC50: 69 nM). After oral dosing, DPZ (ID50: 2.6 mg/kg) inhibited brain ChE dose-dependently without any remarkable effect on ChE in the heart and small intestine, whereas tacrine (ID50: 9.5 mg/kg) inhibited ChE equally in the brain and peripheral tissues. Brain microdialysis revealed that DPZ (2.5 mg/kg) enhanced extracellular ACh concentrations in the cerebral cortex and hippocampus in rats. In behavioral studies, DPZ counteracted both the deficit in passive avoidance induced by lesioning of the nucleus basalis magnocellularis (0.125-1.0 mg/kg) and the impairment in acquisition of a hidden-platform water maze task after lesioning of the medial septum in rats (0.5 mg/kg). DPZ also inhibited the scopolamine-induced impairment of radial maze performance (0.5 mg/kg). Placebo-controlled clinical studies of 12- and 24-week treatments of DPZ (5 mg, 10 mg/day) clearly showed an improvement in cognitive scores of probable AD patients.View full abstractDownload PDF (521K) -
Joji NAKAMURA, Yoshihisa KUWANA, Nobuyuki YUKITOSHI2000 Volume 115 Issue 1 Pages 53-57
Published: 2000
Released on J-STAGE: January 30, 2007
JOURNAL FREE ACCESSTopiramate is a novel antiepileptic drug, a fructopyranose derivative. In animal studies, topiramate suppresses maximal electroshock seizures, whereas it does not exert inhibitory effects on pentylenetetrazol-induced seizures. Since topiramate hardly affects the threshold of the seizure, topiramate has been believed to be a type of antiepileptic drug that blocks spread of seizures. Thus far, the mechanisms of its actions have been proven to include use-dependent inhibition of voltage-dependent Na+ channels in neurons, potentiation of GABA (γ-amino-butyric acid)-induced Cl- influx, and inhibitory effects on inward currents by antagonizing kainate/α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. In clinical studies conducted overseas, topiramate has been demonstrated to be effective in the treatment of partial seizures etc. In 55 countries including UK and USA, topiramate has been already approved for the clinical use as a drug for partial seizures, while a phase III study has been planned in Japan, using patients with symptomatic localization-related epilepsies.View full abstractDownload PDF (368K)
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