Mu and kappa opioid receptor agonists antagonize icilin-induced wet-dog shaking in rats

Icilin is a cooling agent that precipitates vigorous wet-dog shakes in rats after acute i.p. administration. Recent research has emphasized the peripheral agonist properties (e.g. activation of transient receptor potential channels, TRPM8 and TRPA1) of icilin rather than its unusual and pronounced behavioral effects, often classified as quasi-morphine withdrawal. We tested selective opioid receptor agonists against icilin-induced wet-dog shakes in rats. Shaking was antagonized following s.c. pretreatment with the mu agonists, morphine (1, 2, 3 mg/kg) and buprenorphine (0.10 mg/kg) or the kappa agonists, nalfurafine (0.02, 0.04 mg/kg) and U50,488H (5 mg/kg). Pretreatment with ICI 204,448 (1, 5, 10 mg/kg), the peripherally directed kappa agonist, or the delta agonist, SNC 80 (0.30, 1, 3, 10 mg/kg), had no marked effect on the incidence of shaking. We conclude that (a) icilin can trigger shaking via interactions within the central nervous system and (b) mu and kappa opioid receptors are involved in suppressing this stimulant behavior.