Mechanisms of Chloroquine-induced Body-scratching Behavior in Rats: Evidence of Involvement of Endogenous Opioid Peptides

Chloroquine is commonly used in the chemotherapy of malaria fever, and as an antiinflammatory disease-modifying agent in patients with rheumatoid arthritis or systemic lupus erythematosus. Administration of chloroquine (20.0 mg/kg IP) significantly (p < 0.05) increased the frequency of body scratching in rats to 29.5+/-9 in 30 min, compared to saline control animals (6.5+/-2/30 min). Morphine, a mu-opiate receptor agonist (1.0 mg/kg IP), potentiated the chloroquine-induced rat body scratching to 40+/-6.6, while the mu-opiate receptor antagonist, naltrexone (0.25 mg/kg, IP, given 15 min prior) blocked the chloroquine induced body scratching to 4.5+/-2 (p < 0.05 ANOVA). In addition, the frequency of chloroquine (20.0 mg/kg IP)-induced body scratching was significantly reduced to 9.1+/-3 in 30 min in rats rendered tolerant to morphine (p < 0.05 ANOVA) compared to the scratching frequency of 40+/-6.6 in morphine-naive rats. These suggests an involvement of mu-opioid receptors and/or endogenous opioid peptides in chloroquine induced body scratching in rats. Promethazine, a histamine-receptor antagonist (1.0 mg/kg IP, given 15 min prior to chloroquine) and the corticosteroid, dexamethasone (1.0 mg/kg, IP, given 15 min prior) separately and significantly (p < 0.01) inhibited the chloroquine-induced scratching in rats, in a similar manner to clinical studies in malaria. Collectively, the novel results implicate opioidergic mechanisms, and confirm the efficacy of antihistamine and corticosteroids in chloroquine body scratching in rats. It also strongly suggests that the chloroquine-induced body-scratching behavior in the rat may be a useful experimental model for chloroquine-induced pruritus in humans.