Icilin-induced wet-dog shakes in rats are dependent on NMDA receptor activation and nitric oxide production.
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.
Werkheiser
Jennifer
J
Department of Pharmacology, Temple University Health Sciences Center, Philadelphia, PA 19140, USA.
Cowan
Alan
A
Gomez
Teresa
T
Henry
Craig
C
Parekh
Shreya
S
Chau
Sony
S
Baron
David A
DA
Rawls
Scott M
SM
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*
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