Conditioned taste aversion in rats induced by the α₁-adrenoceptor agonist cirazoline

Recent studies have indicated that α₁-adrenoceptor agonists such as phenylpropanolamine (PPA), cirazoline, amidephrine, and SK&F-89748 suppress food intake in rats. These compounds activate α₁-adrenoceptors within the paraventricular hypothalamic nucleus (PVN) and may excite efferent fibers that inhibit feeding. Studies of the effects of α₁-agonists suggest a specificity for feeding behavior, but no study to date has evaluated whether these agonists may suppress feeding behavior by the induction of malaise. Accordingly, the present experiment examined the ability of systemically administered cirazoline (0.1, 0.2, and 0.4 mg/kg, IP) to induce conditioned taste aversion (CTA) to a saccharin solution. Significant CTA was noted for 0.2 and 0.4 mg/kg cirazoline but not for 0.1 mg/kg cirazoline, compared to a vehicle treatment. The ED₅₀ for cirazoline-induced aversion was computed to be 0.3 mg/kg, which contrasts with an ED₅₀ value of 0.09 mg/kg for the effect of cirazoline on food intake (computed in other studies). More importantly, a 0.1 mg/kg dose of cirazoline, which is slightly greater than that of the ED₅₀ value for suppression of feeding, did not induce significant CTA in the present study. These results suggest that malaise is not a prominent factor in the suppressive activity of cirazoline on food intake and advocate the use of cirazoline as an effective appetite suppressant.