The effect of compound 48/80 on the precipitated withdrawal syndrome of dogs

The aim of this study was to eliminate endogenous stores of histamine before inducing the precipitated withdrawal syndrome. Results demonstrate that histamine plays a role in the emergence of some of the symptoms which characterize the precipitated abstinence syndrome in morphine-dependent dogs. Morphine-dependent dogs receiving 0.5 mg/kg n-allyl-normorphine exhibit the precipitated abstinence syndrome. Injection of compound 48/80, 0.5 mg/kg, a potent histamine liberator, produced, on the other hand, typical signs of the abstinence syndrome. A second injection of this compound 24 hours later, however, failed to induce these signs. An injection of n-allyl-normorphine also failed to induce these signs in dogs pretreated with compound 48/80 despite the fact that the dogs were still on their morphine regime. Control experiments on naive animals showed that injection of 0.5 mg/kg n-allyl-normorphine failed to produce signs of the abstinence syndrome. Injection of compound 48/80, a potent histamine liberator, on the other hand, did produce the typical signs of the abstinence syndrome. Animals pretreated with n-allyl-normorphine followed by compound 48/80 responded similarly to animals treated with compound 48/80 alone.