Role of intracellular calcium on the modulation of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes

The role of intracellular calcium in the modifications of naloxone-precipit ated withdrawal jumping in morphine-dependent mice by diabetes was examined . Naloxone-precipitated withdrawal jumping was significantly less in morphi ne-dependent diabetic mice than in morphine-dependent non-diabetic mice. In tracerebroventricular (i.c.v.) pretreatment with ryanodine attenuated nalox one-precipitated withdrawal jumping in morphine-dependent non-diabetic mice . However, naloxone-precipitated withdrawal jumping in morphine-dependent d iabetic mice was not affected by i.c.v. pretreatment with ryanodine. Moreov er, i.c.v. pretreatment with thapsigargin, a Ca2+-ATPase inhibitor, enhance d naloxone-precipitated withdrawal jumping in morphine-dependent non-diabet ic mice, but not in morphine-dependent diabetic mice. The noradrenaline (NA ) turnover in the frontal cortex in morphine-dependent non-diabetic mice, b ut 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 morp hine-dependent non-diabetic mice. These results suggest that increased intr acellular calcium augmented naloxone-precipitated withdrawal jumping and th e turnover rate of NA in the frontal cortex in morphine-dependent non-diabe tic mice. Furthermore, it seems likely that the attenuation of naloxone-pre cipitated withdrawal jumping in morphine-dependent diabetic mice may be due , in part, to the dysfunction of intracellular calcium store. (C) 1999 Else vier Science B.V. All rights reserved.