Pratt J A, Laurie D J, McCulloch J
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, U.K.
Brain Res. 1988 Dec 20;475(2):218-31. doi: 10.1016/0006-8993(88)90610-5.
The effects of the beta-carboline benzodiazepine receptor ligand FG 7142 upon local cerebral glucose utilization have been examined in conscious rats using the quantitative [14C]2-deoxyglucose autoradiographic technique. FG 7142 (1-10 mg/kg i.v.) produced behavioural changes consistent with an anxiogenic action. At the largest dose of FG 7142 (10 mg/kg) 30% of the animals experienced overt convulsions. In the data analysis animals were divided according to the behavioural response elicited by the drug. In animals not expressing convulsions, FG 7142 (1-10 mg/kg) effected increases in glucose utilization in 33 of the 65 regions examined. The majority of changes were confined to limbic structures with pronounced effects occurring in the mammillary body, anterior thalamic nuclei, septal nuclei and the oriens and molecular layers of the hippocampus. Glucose use in other structures associated with auditory and visual processing, such as the medial and lateral geniculate body, and associated cortical areas, was also significantly increased. However, brain regions involved in motor control were minimally affected. The patterns of local cerebral glucose use in animals expressing FG 7142-induced convulsions were contrasted with those from an equivalent non-seizure group. Some limbic structures which were significantly affected by FG 7142 (non-seizure group) displayed a further increase in glucose utilization during convulsions. These included the mammillary body and septum. Many other limbic structures (anterior thalamic nuclei, CA fields of the hippocampus and basolateral amygdala) did not display this further rise in glucose utilization. In the cortical amygdala, lateral preoptic area of the hypothalamus, nucleus accumbens and lateral elevations in glucose utilization were restricted to those animals experiencing overt convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)
已采用定量[¹⁴C]2-脱氧葡萄糖放射自显影技术,在清醒大鼠中研究了β-咔啉苯二氮䓬受体配体FG 7142对局部脑葡萄糖利用的影响。FG 7142(静脉注射1 - 10毫克/千克)产生了与致焦虑作用一致的行为变化。在FG 7142最大剂量(10毫克/千克)时,30%的动物出现明显惊厥。在数据分析中,根据药物引发的行为反应对动物进行分组。在未出现惊厥的动物中,FG 7142(1 - 10毫克/千克)使所检测的65个脑区中的33个脑区的葡萄糖利用增加。大多数变化局限于边缘结构,在乳头体、丘脑前核、隔核以及海马的海马伞和分子层有明显影响。与听觉和视觉处理相关的其他结构,如内侧和外侧膝状体以及相关皮质区域的葡萄糖利用也显著增加。然而,参与运动控制的脑区受影响最小。将出现FG 7142诱导惊厥的动物的局部脑葡萄糖利用模式与同等非惊厥组的模式进行对比。一些受FG 7142显著影响的边缘结构(非惊厥组)在惊厥期间葡萄糖利用进一步增加。这些结构包括乳头体和隔区。许多其他边缘结构(丘脑前核、海马CA区和基底外侧杏仁核)并未出现葡萄糖利用的进一步升高。在皮质杏仁核、下丘脑外侧视前区、伏隔核和外侧隆起,葡萄糖利用的增加仅限于那些出现明显惊厥的动物。(摘要截取自250词)