The effect of stress and adrenalectomy on morphine analgesia and naloxone potency in mice

Abstract

Pretreatment of mice with a single injection of corticosterone increased the potency of naloxone in antagonising the antinociceptive effect of morphine measured 3 h later. Pretreatment with morphine also induced a dose-dependent increase in naloxone potency. Co-administration of corticosterone with a low dose of morphine further augmented the potency of naloxone, but in combination with a higher dose of morphine it failed to cause any further potentiation of naloxone potency. Restraint stress for 1 h also caused an increased in naloxone potency when tested 3 h later, and this was further enhanced when tacrine 5.0 mg/kg was administered immediately after stress. Administration of atropine sulphate 2.0 mg/kg s.c. immediately before restraint abolished the effect of stress in potentiating the naloxone potency. Adrenalectomy sensitised mice to the antinociceptive effect of morphine. Although adrenalectomy only partially interfered with the development of increased naloxone potency after pretreatment with morphine, the augmenting effect of tacrine on naloxone potency was completely abolished. Adrenalectomy did not alter the incidence of jumping precipitated by naloxone in morphine-pretreated mice. Both restraint and corticosterone reduced the withdrawal jumping. It is concluded that the stress component of morphine is only partly responsible for the induction of increase in naloxone potency. There is an apparent interaction between central cholinergic mechanisms and stress in the induction of this increased naloxone potency. The phenomenon of increased naloxone antagonism may not be related to the development of acute dependence on morphine.