Peripheral Nmda Receptor/No System Blockage Inhibits Itch Responses Induced by Chloroquine in Mice Publisher Pubmed



Haddadi NS^{1, 2, 4} ; Foroutan A^{1, 3} ; Ostadhadi S^{1, 2, 5} ; Azimi E⁶ ; Rahimi N^{1, 2} ; Nateghpour M⁴ ; Lerner EA⁶ ; Dehpour AR^{1, 2, 3}
Source: Acta Dermato-Venereologica Published:2017

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 (LNAME), decreases CQ-induced scratching 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 CQinduced scratching behavior. © 2017 Acta Dermato-Venereologica.