title: Peripheral NMDA Receptor/NO System Blockage Inhibits Itch Responses Induced by Chloroquine in Mice.
abstract: Intradermal administration of chloroquine (CQ) provokes scratching behavior in mice. Chloroquine-induced itch is histamine-independent and we have reported that the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway is involved in CQ-induced scratching behavior in mice. Previous studies have demonstrated that activation of N-methyl-d-aspartate receptors (NMDARs) induces NO production. Here we show that NMDAR antagonists significantly decrease CQ-induced scratching in mice while a non-effective dose of an NMDAR agonist potentiates the scratching behavior provoked by sub-effective doses of CQ. In contrast, combined pre-treatment with sub-effective doses of an NMDAR antagonist, MK-801, and the NO synthase inhibitor, L-N-nitro arginine methyl ester (L-NAME), decreases CQ-induced scrat-ching behavior. While intradermal administration of CQ significantly increases the concentration of intradermal nitrite, the end product of NO metabolism, effective doses of intraperitoneal and intradermal MK-801 significantly decrease intradermal nitrite levels. Likewise, administration of an effective dose of L-NAME significantly decreases CQ-induced nitrite production. We conclude that the NMDA/NO pathway in the skin modulates CQ-induced scratching behavior.
authors.affiliation: Experimental Medicine Research Center, Tehran University of Medical Sciences, 13145-784 Tehran, Iran.
authors.forename: Nazgol-Sadat
authors.initials: NS
authors.lastname: Haddadi
authors.forename: Arash
authors.initials: A
authors.lastname: Foroutan
authors.forename: Sattar
authors.initials: S
authors.lastname: Ostadhadi
authors.forename: Ehsan
authors.initials: E
authors.lastname: Azimi
authors.forename: Nastaran
authors.initials: N
authors.lastname: Rahimi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Nateghpour
authors.forename: Ethan A
authors.initials: EA
authors.lastname: Lerner
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002738:Chloroquine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D039563:Histamine H1 Antagonists, Non-Sedating / Q000494:pharmacology; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D011537:Pruritus / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D039563:Histamine H1 Antagonists, Non-Sedating; D009573:Nitrites; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D002738:Chloroquine; D019001:Nitric Oxide Synthase