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- Title
Neuronal protein kinase Cγ-dependent proliferation and hypertrophy of spinal cord astrocytes following repeated in vivo administration of morphine.
- Authors
Narita, Minoru; Suzuki, Masami; Narita, Michiko; Yajima, Yoshinori; Suzuki, Ryusuke; Shioda, Seiji; Suzuki, Tsutomu
- Abstract
Repeated administration of morphine induced a time-dependent inhibition of the morphine-induced antinociceptive action, indicating the development of tolerance to morphine. We demonstrated that mice tolerant to morphine exhibited a significant increase in the level of protein kinase Cγ-like immunoreactivity (PKCγ-IR) in the dorsal horn of the spinal cord. The PKCγ-IR was exclusively colocalized with the neuron-specific markers neuronal nuclei (NeuN) and microtubule associated protein 2ab (MAP2ab). Here we found a dramatic increase in reactive astrocytes in the dorsal horn of the spinal cord following repeated treatment with morphine, as characterized by the increase and morphological changes in glial fibrillary acidic protein (GFAP)-positive cells. Furthermore, transgenic mice that express enhanced green fluorescent protein (EGFP) under the control of the mouse GFAP promoter displayed enhanced levels of EGFP expression after repeated treatment with morphine. Under these conditions, mice lacking the PKCγ gene failed to show any changes in astroglial hypertrophy or proliferation after repeated treatment with morphine. These findings strongly support the idea that the sustained activation of neuronal PKCγ is implicated in the increased levels of reactive astrocytes in the dorsal horn of the spinal cord following repeated treatment with morphine. This neuron–glia communication may lead to the development of tolerance to morphine-induced antinociception.
- Subjects
GREEN fluorescent protein; CENTRAL nervous system; PROTEIN kinases; MORPHINE; TRANSGENIC mice; MICROTUBULES; NEUROGLIA; ASTROCYTES
- Publication
European Journal of Neuroscience, 2004, Vol 19, Issue 2, p479
- ISSN
0953-816X
- Publication type
Article
- DOI
10.1111/j.0953-816X.2003.03119.x