Changes in local cerebral glucose utilization induced by the beta-carbolines FG 7142 and DMCM reveal brain structures involved in the control of anxiety and seizure activity

Abstract

The brain regions that may be functionally involved in the control of anxiety and the development of seizures were examined using quantitative 1-14C-deoxyglucose autoradiography. For this purpose, beta-carbolines FG 7142 and DMCM were employed. They exert their effects via the benzodiazepine receptor, and whereas both possess anxiogenic properties, FG 7142 is a proconvulsant and DMCM a potent convulsant. The pattern of increases of local cerebral glucose utilization (LCGU) induced by FG 7142 was mainly restricted to limbic structures, such as the lateral septal nucleus, the anterior thalamic nuclei, and the mamillary nuclei. However, structures involved in motor regulation were also affected. A pronounced increase in LCGU was observed in the posterior part of the substantia nigra, pars reticulata. Further, the LCGU of the globus pallidus, the ventral thalamic nucleus, and the cerebellum was increased. DMCM likewise increased LCGU of the mamillary body and the lateral septal nucleus. In contrast to FG 7142, the hippocampal formation displayed an increase in LCGU, while LCGU of the anterior thalamic nuclei was unchanged. A pronounced increase in LCGU was seen in the substantia nigra, pars reticulata in addition to other structures functionally involved in central motor regulation. The specific benzodiazepine antagonist Ro 15-1788 antagonized the effects of both FG 7142 and DMCM. It is concluded that the beta-carbolines FG 7142 and DMCM produce selective effects upon LCGU that are mediated by benzodiazepine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)