AVOIDANCE ENHANCEMENT AND DISCRIMINATIVE RESPONSE CONTROL BY ANXIOLYTICS WITH DRUGS ACTING ON THE GABA SYSTEM
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概要
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Two types of conditioned behaviors were investigated for the purpose of evaluating anxiolytic drugs. A conditioning procedure used was an active avoidance in poorly-performing mice. Chlordiazepoxide, diazepam, chlorazepate and meprobamate increased the avoidance rate, while chlorpromazine, haloperidol and nortriptyline did not produce such an effect. The effect of diazepam was potentiated by γ-aminobutyric acid (GABA) and aminoxyacetic acid (AOAA) and antagonized by picrotoxin and thiosemicarbazide, but was influenced little by spiroperidol, α-methyltyrosine, phenoxy-benzamine and levallorphan. In addition, the effect of other anxiolytics was potentiated by AOAA and antagonized by picrotoxin. Biperiden, methamphetamine, caffeine and morphine also induced an avoidance enhancement, which was not influenced by AOAA. A drug discrimination experiment was also performed using a milk-reinforced two-lever operant method. In the rats trained to discriminate phenobarbital from saline, diazepam produced a dose-related phenobarbital-lever selection, which was potentiated by AOAA and antagonized by picrotoxin. Chlordiazepoxide, chlorazepate and meprobamate also elicited responses on the phenobarbital-lever. On the other hand, haloperidol, nortriptyline, biperiden, methamphetamine, caffeine and morphine produced a saline-lever selection, at the doses tested. These results suggest that, among several drugs tested, the avoidance enhancement and discriminative response control by anxiolytics may be closely linked with the GABA system.
- 社団法人 日本薬理学会の論文
著者
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Oka Makoto
Department Of Physics H-27 Tokyo Institute Of Technology
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YOSHIDA KOUICHI
Department of Pharmacology, Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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SHIMIZU MASANAO
Department of Pharmacology, Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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Shimizu Masanao
Department Of Pharmacology Research Laboratories Dainippon Pharmaceutical Co. Ltd.
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YAMADA Kiyoko
Department of Pharmacology, Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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Yoshida Kouichi
Department Of Pharmacology Research Laboratories Dainippon Pharmaceutical Co. Ltd.
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Yamada Kiyoko
Department Of Oral Health Science Section Of Dental Materials And Engineering Graduate School Of Den
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OKA Makoto
Department of Pharmacology, Research Laboratories, Dainippon Pharmaceutical Co., Ltd.
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