Development of physical dependence on morphine not accompanied with tolerance formation.

The development of tolerance induced by daily repeated administration of 10 mg/kg of s.c. morphine was suppressed by combined injection of adrenergic blockers, 10 mg/kg i.p. phentolamine or propranolol, in mice. However, this treatment could not prevent the development of physical dependence as evidenced by the naloxone precipitated abstinence signs. Thus, we provide a new evidence that morphine analgesia, tolerance and physical dependence is dissociable from each other.