Effects of N omega-nitro-L-arginine methyl ester on benzodiazepine binding in some limbic areas of hyperlipidaemic rats.
Quantitative autoradiography techniques were used to evaluate the chronic effects of the potent nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, on the binding pattern of [3H]flunitrazepam (benzodiazepine agonist) in some behaviorally key limbic areas of the genetic hyperlipidaemic Pittsburg Yoshida rat. Administration of this potent synthase inhibitor was capable of supplying higher and moderately higher binding levels in the basolateral amygdala nucleus (+52%) and in the oriens-pyramidalis CA1 hippocampus layer (+38%), respectively. When we tested for the binding changes in the presence of GABA (principal benzodiazepine modulator) we noticed that a physiological concentration (20 microM) of this inhibitory neurotransmitter was sufficient to induce notable changes in other limbic areas. In fact, lower binding values (-65%) were reported for the bed nucleus of stria terminalis whereas moderately higher values (+38%) were obtained for the radiatum-lacunosum molecular CA1 hippocampus layer. From the saturation studies, it was possible to observe that the major receptor variations provoked by the potent synthase inhibitor were not only due to changes in the total number of binding sites because there were variations, as in the case of the basolateral amygdala nucleus, that were instead due to differences in the affinity binding state. These results provide evidences of a GABAergic-nitric oxide synthase inhibitor interaction that might also be involved in the regulation of convulsive, anxiolytic, and aggressive behaviors that are modulated at the benzodiazepine site.
Facciolo
R M
RM
Department of Ecology, University of Calabria, Cosenza, Italy.
Tavolaro
R
R
Chinellato
A
A
Ragazzi
E
E
Canonaco
M
M
Fassina
G
G
D000818:Animals; D001345:Autoradiography; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005445:Flunitrazepam / Q000493:pharmacokinetics / Q000494:pharmacology; D018757:GABA Modulators / Q000493:pharmacokinetics / Q000494:pharmacology; D006949:Hyperlipidemias / Q000378:metabolism*; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D018757:GABA Modulators; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester