Chronic morphine treatment increases the expression of vesicular glutamate transporter 1 in the mouse spinal cord.

Long-term exposure to morphine results in tolerance to morphine-induced antinociception. Here, we found that mice tolerant to morphine exhibited the significant increase in the protein levels of the vesicular glutamate transporter 1 and the synaptic vesicle-specific small G protein Rab3A, but not vesicular glutamate transporter 2 and vesicular gamma-aminobutyric acid transporter. These findings suggest that repeated treatment with morphine enhances excitatory synaptic transmission in the spinal cord, and in turn suppresses the morphine-induced antinociception.