EFFECT OF N-G-NITRO-L-ARGININE METHYL-ESTER, A NITRIC-OXIDE SYNTHASE INHIBITOR, ON NEUROTRANSMITTER RECEPTOR SYSTEMS IN AGED RATS

In order to examine the effect of age and nitric oxide synthase inhibi tor, N-G-nitro-L-arginine methyl ester (L-NAME), we studied the change s on major neurotransmitter receptor systems in 6 (adult) and 24-month -old (aged) Fischer male rats using receptor autoradiography. L-NAME w as administrated intraperitoneally in aged rats once a day for 3 weeks . [H-3]QNB (quinuclidinyl benzilate), [H-3]HC (hemicholinium-3), [H-3] muscimol, [H-3]SCH 23390 ,5-tetrahydro-3-methyl-5-phenyl-7-ol-benzazep ine), [H-3]nemonapride and [H-3]mazindol were used as markers of musca rinic acetylcholine receptors, high-affinity choline uptake sites, GAB A(A) (gamma-aminobutyric acid(A)) receptors, dopamine D-1 receptors, d opamine D-2 receptors and dopamine uptake sites, respectively. The age -related change in [H-3]muscimol binding in the brain was more pronoun ced than that in [H-3]QNB, [H-3]HC, [H-3]SCH 23390, [H-3]nemonapride a nd [H-3]mazindol binding. Chronic treatment (4 weeks) with L-NAME caus ed no significant changes in [H-3]QNB, [H-3]muscimol, [H-3]SCH 23390 a nd [H-3]nemonapride binding in most areas of aged rat brain, as compar ed with vehicle-treated aged animals. However, chronic treatment with L-NAME caused a significant reduction in [H-3]HC and [H-3]mazindol bin ding in any brain regions of aged rats in comparison with the vehicle- treated aged animals. These results demonstrate that the GABAergic sys tem is more susceptible to aging processes than cholinergic and dopami nergic systems in the brain. Furthermore, our findings suggest that ni tric oxide may play some role in the regulation of choline uptake and dopamine uptake systems during aging processes. Eur J Neurol 5:601-608 (C) 1998 Lippincott Williams & Wilkins.