EFFECTS OF N-OMEGA-NITRO-L-ARGININE METHYL-ESTER ON BENZODIAZEPINE BINDING IN SOME LIMBIC AREAS OF HYPERLIPIDEMIC RATS

Quantitative autoradiography techniques were used to evaluate the chro nic effects of the potent nitric oxide synthase inhibitor, N omega-nit ro-L-arginine methyl ester, on the binding pattern of [H-3]flunitrazep am (benzodiazepine agonist) in some behaviorally key limbic areas of t he genetic hyperlipidaemic Pittsburg Yoshida rat. Administration of th is potent synthase inhibitor was capable of supplying higher and moder ately higher binding levels in the basolateral amygdala nucleus (+52%) and in the oriens-pyramidalis CA1 hippocampus layer (+38%), respectiv ely. When we tested for the binding changes in the presence of GABA (p rincipal benzodiazepine modulator) we noticed that a physiological con centration (20 mu M) of this inhibitory neurotransmitter was sufficien t to induce notable changes in other limbic areas. In fact, lower bind ing values (-65%) were reported for the bed nucleus of stria terminali s whereas moderately higher values (+38%) were obtained for the radiat um-lacunosum molecular CAI hippocampus layer. From the saturation stud ies, it was possible to observe that the major receptor variations pro voked by the potent synthase inhibitor were not only due to changes in the total number of binding sites because there were variations, as i n the case of the basolateral amygdala nucleus, that were instead due to differences in the affinity binding state. These results provide ev idences of a GABAergic-nitric oxide synthase inhibitor interaction tha t might also be involved in the regulation of convulsive, anxiolytic, and aggressive behaviors that are modulated at the benzodiazepine site .