Clonidine antagonizes naloxone-induced suppression of conditioned behavior and body weight loss in morphine-dependent rats.

Clonidine's action on naloxone (Nx)-induced suppression of fixed-ratio (FR15) responding and body weight loss was studied in morphine (M)-dependent rats. Clonidine (10--70 microgram/kg IP) injected 30 min prior to the behavioral session resulted in a dose-related suppression of operant behavior in M-naive animals. A small, but significant decrease (3--5%) in body weight was also observed at the higher doses of clonidine. More than twice as much weight loss, associated with diarrhea, was obtained when Nx (5.0 mg/kg IP) was administered to M-dependent animals. When clonidine (10--50 microgram/kg IP) was administered prior to Nx, in M-dependent animals, the withdrawal-induced disruption of operant responding was significantly attenuated. Concurrent weight loss, which was significantly antagonized by 1 microgram clonidine/kg, was decreased by as much as 40 percent. The degree of amelioration of withdrawal that was observed appeared to be inversely related to the dose of clonidine. The optimal dose was 10 microgram/kg, which by itself was only partially behaviorally active. At higher doses, clonidine's blocking properties were less apparent as a result of its own potent behavioral suppressant and diuretic effects which masked its capacity to attenuate withdrawal. The data are discussed in relation to the application of operant technics for assessing drug treatment(s) designed to alter the severity of narcotic withdrawal.