An increase in
GABA uptake by isolated rat brain synaptic endings as well as a decrease of pharmacologically active
GABA analogue
muscimol specific binding have indicated a physiologically drastic failure in realization of
GABA-mediated inhibitory effects in CNS induced by
diabetic encephalopathy. In spite of the impairment of inhibitory function of GABAergic transmission in diabetes a crucial activation of
benzodiazepine receptors was determined, as it is tested by the increase in specific binding of
flunitrazepam by synaptic membranes. This increase may play an important role in endogenous control of neural activity associated with the factors undefined so far. Using the approach that
GABA, and several synthetic
GABA agonists, appear to increase the affinity of the
benzodiazepine recognition sites for such
ligands, presumably by some allosteric mechanism, the findings concerning the in vitro binding assay technique confirm at least some of the functional characteristics observed between
GABA and
benzodiazepine receptors in vivo under pathological conditions. Indeed, the absence of activating effect on the affinity of
flunitrazepam specific binding in the presence of micromolar concentrations of exogenous
GABA implicate diabetes-induced alterations in coupling
GABA- and
benzodiazepine receptors that might be linked to changes in conformantial state of this membrane-bound complex and could partially explain diabetes-induced impairments of GABAergic transmission evaluated in the present study. Our study suggests that
nicotinamide and especially
GABA play an important role in improving the functioning of brain
GABA-
benzodiazepine complex impaired in diabetes through specific
ligand-mediated mechanism and can be useful in the management of diabetes-associated brain failures.