title: Icilin-induced wet-dog shakes in rats are dependent on NMDA receptor activation and nitric oxide production.
abstract: Icilin is a cold channel agonist that produces vigorous wet-dog shaking in rats. The shaking is accompanied by an increase in the level of extracellular glutamate in the brain. Hence, we hypothesized that icilin-induced wet-dog shakes are dependent on increased glutamatergic transmission and nitric oxide (NO) production. Rats injected with icilin (0.5, 1, 2.5, 5 mg/kg, i.p.) displayed a dose-related increase in wet-dog shakes. Pretreatment with LY 235959 (1, 2 mg/kg, i.p.), a NMDA receptor antagonist, or L-NAME (50 mg/kg, i.p.), a NO synthase (NOS) inhibitor, attenuated icilin-induced wet-dog shakes. The shaking was also reduced by intracerebroventricular L-NAME (1 mg/rat, i.c.v.) administration, indicating that the stimulant effect of icilin is dependent on central NO production. Pretreatment with 6,7-dinitroquinoxaline-2,3(1H,4H)-dione (DNQX) (10, 20 mg/kg, i.p.), an AMPA receptor antagonist, or ceftriaxone (200 mg/kg, i.p. for 5 days), a beta-lactam antibiotic and glutamate transporter subtype 1 (GLT-1) activator, did not alter the incidence of icilin-induced shaking. The present data reveal that icilin produces behavioral stimulation by a mechanism requiring NMDA receptor activation and nitric oxide production and suggest that glutamate and NO signaling play important roles in cold channel pharmacology.
authors.affiliation: Department of Pharmacology, Temple University Health Sciences Center, Philadelphia, PA 19140, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Werkheiser
authors.forename: Alan
authors.initials: A
authors.lastname: Cowan
authors.forename: Teresa
authors.initials: T
authors.lastname: Gomez
authors.forename: Craig
authors.initials: C
authors.lastname: Henry
authors.forename: Shreya
authors.initials: S
authors.lastname: Parekh
authors.forename: Sony
authors.initials: S
authors.lastname: Chau
authors.forename: David A
authors.initials: DA
authors.lastname: Baron
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011744:Pyrimidinones / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D014202:Tremor / Q000139:chemically induced*
chemical_list: D004791:Enzyme Inhibitors; D011744:Pyrimidinones; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; C490483:icilin; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester