OPIATE TOLERANCE-INDUCED MODULATION OF FREE INTRACELLULAR CALCIUM IN SYNAPTOSOMES

Synaptosomes were prepared from morphine-tolerant and non-tolerant mice. Significantly higher levels of basal free intracellular calcium were observed in the synaptosomes from the opiate-tolerant mice compared to synaptosomes from non-tolerant mice (468 nM versus 328 nM, respectively). In addition, morphine (1-mu-M) failed to attenuate KCl-induced rises in intracellular calcium in the synaptosomes from the tolerant mice. Conversely, morphine produced a concentration-related, naloxone-reversible attenuation of 50 mM KCl-induced rises in intracellular calcium in the synaptosomes from the non-tolerant mice. Omega conotoxin, which blocks both "L" and "N" type calcium channels, attenuated KCl-stimulated rises in intracellular calcium only in synaptosomes from non-tolerant mice. BAY-K 8644, an "L-type" calcium channel agonist, produced nifedipine-reversible increases in intracellular calcium in the synaptosomes from the tolerant animals only. These data suggest that chronic exposure to morphine results in an alteration in either the number or the activation state of calcium channels in the membrane. Changes in intracellular free calcium may be the final common pathway through which neurons adapt to the chronic exposure to morphine.