Changes in sensitivity to apomorphine during morphine dependence and withdrawal in rats

Abstract

Stereotyped behavior induced by injection of apomorphine hydrochloride (10 mg/kg i.p) was measured in control rats, rats made dependent on morphine and dependent rats undergoing naloxone-precipitated withdrawal. The dose of apomorphine chosen was approximately the ED50 dose, so that changes in sensitivity to apomorphine in either direction could be determined. Rats which had received a subcutaneous morphine (75 mg) pellet implant 72 hours previously demonstrated an increased sensitivity to apomorphine when compared with placebo-implanted controls. During withdrawal precipitated by injection of naloxone hydrochloride (0.2 mg/kg i.p.) this increased sensitivity disappeared. Naloxone alone, in a dose of 1.0 mg/kg but not 0.2 mg/kg, significantly antagonized apomorphine-induced stereotyped behavior and these effects of apomorphine were also reduced by an acute injection of morphine sulfate (10 mg/kg). The significance of these findings with regard to changes in central dopaminergic systems during dependence and withdrawal is discussed.