Morphine analgesia, tolerance and physical dependence in the adrenalectomized rat

1. Adrenalectomy reduced the median antinociceptive dose (AD50) of morphine in male Sprague-Dawley rats. The antinociceptive effect was assessed by the tail-flick method of D'Amour & Smith (1941).2. Tolerance to the antinociceptive effect of morphine developed in adrenalectomized and sham-operated rats after chronic exposure to morphine. Development of tolerance did not significantly alter the increased sensitivity of adrenalectomized rats to the antinociceptive effect of morphine.3. Adrenal weights were not increased in rats rendered physically dependent on morphine by subcutaneous implantation of a morphine pellet. Withdrawal, induced by intraperitoneal injection of naloxone hydrochloride, 4 mg/kg, or by removal of the implanted pellet, resulted in a rapid increase in adrenal weight.4. In morphine-dependent animals, the incidence of abstinence signs and body weight loss during precipitated withdrawal did not appear to be significantly influenced by adrenalectomy or by corticosterone-pretreatment.