The role of intracellular calcium in the modifications of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes was examined. Naloxone-precipitated withdrawal jumping was significantly less in morphine-dependent diabetic mice than in morphine-dependent non-diabetic mice. Intracerebroventricular (i.c.v. ) pretreatment with ryanodine attenuated naloxone-precipitated withdrawal jumping in morphine-dependent non-diabetic mice. However, naloxone-precipitated withdrawal jumping in morphine-dependent diabetic mice was not affected by i.c.v. pretreatment with ryanodine. Moreover, i.c.v. pretreatment with thapsigargin, a Ca2+-ATPase inhibitor, enhanced naloxone-precipitated withdrawal jumping in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice. The noradrenaline (NA) turnover in the frontal cortex in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was significantly increased by naloxone injection. Naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was blocked by i.c.v. pretreatment with ryanodine. In contrast to ryanodine, thapsigargin enhanced naloxone-induced enhancement of NA turnover in morphine-dependent non-diabetic mice. These results suggest that increased intracellular calcium augmented naloxone-precipitated withdrawal jumping and the turnover rate of NA in the frontal cortex in morphine-dependent non-diabetic mice. Furthermore, it seems likely that the attenuation of naloxone-precipitated withdrawal jumping in morphine-dependent diabetic mice may be due, in part, to the dysfunction of intracellular calcium store.
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