Nitric oxide synthase inhibitors enhance 5-HT2 receptor-mediated behavior, the head-twitch response in mice.
The purpose of this study was to characterize behavioral interactions between nitric oxide synthase (NOS) inhibitors and serotonergic 5-HT2 receptors. In the present study, NOS inhibitors, N(G)-nitro-L-arginine, N(G)-nitro-L-arginine methylester, N(G)-monomethyl-L-arginine, 7-nitroindazole, trifluoperazine and NO scavenger, methylene blue markedly enhanced 5-hydroxytryptamine (5-HT)-induced selective serotonergic behavior, the head twitch response (HTR), in mice. However NO generators, sodium nitroprusside, 3-morpholinosydnonimine and S-nitroso-N-acetylpenicillamine as well as NO precursor, L-arginine markedly inhibited 5-HT induced HTR in mice. In the previous study, it was demonstrated that the N-methyl-D-aspartate (NMDA) receptor antagonists markedly enhanced 5-HT-induced selective serotonergic behavior, HTR, whereas NMDA itself inhibited 5-HT-induced HTR in mice. In the present study, it was demonstrated that the inhibition by a NMDA receptor agonist, NMDA of 5-HT-induced HTR was reversed by the treatment with NOS inhibitors, N(G)-nitro-L-arginine and N(G)-nitro-L-arginine methylester. The suppressive action by a NO generator, S-nitroso-N-acetylpenicillamine of 5-HT-induced HTR was also reversed by the treatment with NMDA receptor antagonists, MK-801 and dextromethorphan. These results have shown that the NO system is located down stream of NMDA receptors involved in modulation of 5-HT2-mediated HTR. Therefore, the enhanced effects of NOS inhibitors on 5-HT-induced HTR support experimental evidence for the NO/5-HT2 as well as NMDA/5-HT2 receptor interactions indicating that NO plays an important role in the glutamatergic modulation of the serotonergic function at the 5-HT2 receptor.
College of Pharmacy, Chungbuk National University, Cheongju, Korea. hskim@trut.chungbuk.ac.kr
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D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003915:Dextromethorphan / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D019416:Head Movements / Q000187:drug effects*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D011985:Receptors, Serotonin; C110881:S-nitro-N-acetylpenicillamine; D012702:Serotonin Antagonists; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; C002385:linsidomine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D003915:Dextromethorphan; D001120:Arginine; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D010396:Penicillamine; D008751:Methylene Blue