title: Endogenous nitric oxide decreases hippocampal levels of serotonin and dopamine in vivo.
abstract: Nitric oxide (NO) modulates the levels of various neurotransmitters in the CNS. Here we determined whether the specific nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI), the non-selective inhibitor of guanylate cyclase (GC) and NOS, methylene blue (MB), the NO-precursor L-arginine (L-Arg), and the selective soluble GC inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) affect extracellular levels of serotonin (5-HT), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) in the rat ventral hippocampus by using microdialysis in freely moving animals. Local perfusion of 7-NI (1 mM) and MB (1 mM) significantly increased extracellular level of 5-HT, whereas DA was increased by 7-NI only. Systemic administration of 7-NI (50 mg kg(-1)) and MB (30 mg kg(-1)) increased the extracellular levels of 5-HT and DA. Extracellular levels of 5-HIAA was not influenced by local or systemic MB or 7-NI. In contrast, extracellular level of HVA was decreased by systemic MB and retrodialyzed MB, but was not influenced by 7-NI. Retrodialysis of L-Arg (2 mM) decreased the levels of 5-HT, DA, 5-HIAA and HVA in the hippocampus. Systemic administration of L-Arg (250 mg kg(-1)) decreased the level of 5-HT, but failed to influence DA, 5-HIAA and HVA. Local perfusion of ODQ (400 microM) did not affect 5-HT overflow in the hippocampus. We conclude that NOS inhibitors increased extracellular levels of 5-HT and DA in the rat ventral hippocampus after local or systemic administration, whereas the NO precursor L-Arg had the opposite effect. Thus, endogenous NO may exert a negative control over the levels of 5-HT and DA in the hippocampus. However, this effect is probably not mediated by cyclic GMP.
authors.affiliation: Department of Biological Psychiatry, Institute for Basic Psychiatric Research, Skovagervej 2, DK-8240 Risskov, Denmark. wegener@dadlnet.dk
authors.forename: G
authors.initials: G
authors.lastname: Wegener
authors.forename: V
authors.initials: V
authors.lastname: Volke
authors.forename: R
authors.initials: R
authors.lastname: Rosenberg
mesh_terms: D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D007191:Indazoles / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D017551:Microdialysis; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D004791:Enzyme Inhibitors; D007191:Indazoles; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D008751:Methylene Blue; C080122:7-nitroindazole; D004298:Dopamine