Inhibition by 8-hydroxy-2-(di-n-propylamino) tetralin and SM-3997, a novel anxiolytic drug,of the hippocampal rhythmical slow activity mediated by 5-hydroxytryptamine1A receptors |
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Authors: | A. Hirose R. Tsuji H. Shimizu T. Tatsuno H. Tanaka Y. Kumasaka M. Nakamura |
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Affiliation: | (1) Research Laboratories, Sumitomo Pharmaceuticals Co., Ltd., 3-1-98, Kasugadenaka, Konohana-ku, 554 Osaka, Japan |
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Abstract: | Summary Electrophysiological studies using spectral analysis techniques were undertaken in rabbits to determine whether or not hippocampal rhythmical slow activity (RSA, theta wave activity) was affected by the 5-hydroxytryptamine1A (5-HT1A) agonists 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and 3 , 4 , 7 , 7 -hexahydro-2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-4, 7-methano-IH-isoindole-1,3(2H)-dione dihydrogen citrate (SM-3997, a newly synthesized anxiolytic drug). Intravenous administration of 8-OH-DPAT and SM-3997 induced a desynchronized pattern with low-amplitude slow wave activity in the hippocampal EEG and inhibited RSA generation following stimulation of the midbrain reticular formation. RSA was also inhibited by 5-HT1A related anxiolytics such as buspirone, gepirone, and ipsapirone. The effects of 8-OH-DPAT and SM-3997 on the hippocampal RSA were blocked by pindolol, which has 5-HT1A antagonistic activity. Direct microinjection of these 5-HTIA selective agonists into the hippocampus inhibited generation of the hippocampal RSA. These findings indicated that 8-OH-DPAT and SM-3997 inhibited the hippocampal RSA by acting on hippocampal 5-HTIA receptors.Send offprint requests to A. Hirose at the above address |
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Keywords: | 8-OH-DPAT 5-HT1A related anxiolytics Hippocampal RSA Power spectrum Rabbit |
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