Effect of NG-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 inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), we studied the changes on major neurotransmitter receptor systems in 6 (adult) and 24-month-old (aged) Fischer male rats using receptor autoradiography. L-NAME was administrated intraperitoneally in aged rats once a day for 4 weeks. [3H]QNB (quinuclidinyl benzilate), [3H]HC (hemicholinium-3), [3H]muscimol, [3H]SCH 23390 ([N-methyl-3H]R[+]-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-7-ol-benzazepine), [3H]nemonapride and [3H]mazindol were used as markers of muscarinic acetylcholine receptors, high-affinity choline uptake sites, GABAA (gamma-aminobutyric acidA) receptors, dopamine D1 receptors, dopamine D2 receptors and dopamine uptake sites, respectively. The age-related change in [3H]muscimol binding in the brain was more pronounced than that in [3H]QNB, [3H]HC, [3H]SCH 23390, [3H]nemonapride and [3H]mazindol binding. Chronic treatment (4 weeks) with L-NAME caused no significant changes in [3H]QNB, [3H]muscimol, [3H]SCH 23390 and [3H]nemonapride binding in most areas of aged rat brain, as compared with vehicle-treated aged animals. However, chronic treatment with L-NAME caused a significant reduction in [3H]HC and [3H]mazindol binding in any brain regions of aged rats in comparison with the vehicle-treated aged animals. These results demonstrate that the GABAergic system is more susceptible to aging processes than cholinergic and dopaminergic systems in the brain. Furthermore, our findings suggest that nitric oxide may play some role in the regulation of choline uptake and dopamine uptake systems during aging processes. Copyright 1998 Lippincott Williams & Wilkins
Araki
T
Department of Neurology, Tohoku University School of Medicine, Sendai and Medicinal Research Group II, Kazusa Research Laboratories, Tokyo Tanabe Co. Ltd, Tokyo, Japan.
Oshima
Y
Kato
H
Shuto
K
Itoyama
Y