Increase of cyclic GMP in cerebellum by methyl-6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM).

The intraperitoneal administration of DMCM (0.5-3 mg/kg) produced a dose-related increase in the content of cyclic GMP in the rat cerebellar cortex. The effect of DMCM on cyclic GMP was abolished by pretreatment with benzodiazepine receptor ligands, diazepam and Ro15-1788 and by the GABA agonist muscimol. The results suggest that DMCM increases cerebellar cyclic GMP content through a direct action on benzodiazepine receptors located in the cerebellar cortex. The interaction between DMCM and the GABAergic system associated with benzodiazepine receptors is discussed. Cerebellar cyclic GMP content can be used as a biochemical index to differentiate agonists and antagonists for benzodiazepine receptors.