RELATIONSHIPS BETWEEN BENZODIAZEPINE RECEPTORS, IMPAIRMENT OF GABAERGIC TRANSMISSION AND CONVULSANT ACTIVITY OF BETA-CCM - A PET STUDY IN THE BABOON PAPIO-PAPIO

被引:7
作者
CHAVOIX, C
BROUILLET, E
KUNIMOTO, M
DELASAYETTE, V
KHALILIVARASTEH, M
HANTRAYE, P
DODD, RH
GUIBERT, B
PRENANT, C
NAQUET, R
MAZIERE, M
机构
[1] CEA,SERV HOSP FREDERIC JOLIOT,DEPT BIOL,F-91406 ORSAY,FRANCE
[2] CNRS,DEPT NEUROPHYSIOL APPLIQUEE,PHYSIOL NERVEUSE LAB,F-91190 GIF SUR YVETTE,FRANCE
[3] CNRS,INST CHIM SUBST NAT,F-91190 GIF SUR YVETTE,FRANCE
关键词
GABA; BENZODIAZEPINE RECEPTORS; BETA-CCM; EPILEPSY; BABOON PAPIO-PAPIO; POSITRON EMISSION TOMOGRAPHY;
D O I
10.1016/0920-1211(91)90030-J
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Central type benzodiazepine receptors were studied in vivo by positron emission tomography in brain areas of 2 different groups of the baboon Papio papio: non-photosensitive (group 1) and those with an allylglycine-induced decrease in GABA-mediated inhibition (group 2). Further, a naturally photosensitive Papio papio (+3 level of photosensitive response) was compared to both groups. Regional brain binding of the specific benzodiazepine receptor ligand, [C-11]Ro 15-1788, was not significantly different between groups 1 and 2. In addition, the data from the naturally photosensitive Papio papio did not seem to differ markedly from groups 1 and 2 either. Pharmacological effects of increasing doses of beta-CCM (0.05-3 mg/kg i.v.) and regional benzodiazepine receptor occupancy by the drug were simultaneously studied using electroencephalographic activity recording and positron emission tomography. A positive correlation was observed between the degree of photosensitivity of the baboon and sensitivity to the action of beta-CCM, with increasing convulsant efficacy of beta-CCM in going from group 1 to the naturally photosensitive baboon, then to group 2. Dose-related displacement curves of [C-11]Ro 15-1788 binding by beta-CCM revealed that reduction in brain GABA concentration did not modify the inhibitory potency of beta-CCM on [C-11]Ro 15-1788 binding in cerebral cortex. This suggests a lack of detectable in vivo allosteric effects of GABA on beta-CCM binding during beta-CCM-induced seizures. Thus, a given dose of beta-CCM displayed increasing pharmacological potency in going from baboons with the lowest photosensitivity to those with the highest, whereas benzodiazepine receptor occupancy by beta-CCM was similar in the cerebral cortex of the different baboons. Conversely, a given level of convulsant activity of beta-CCM was related to a different benzodiazepine receptor occupancy by the drug, depending on the photosensitivity of Papio papio. A given dose of a drug may, thus, have a different pharmacological potency when occupying the same number of receptors, depending on the physiopathological state of the subject.
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页码:1 / 10
页数:10
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