Abstract
The activation of spinal cord N-methyl-D-aspartate (NMDA) receptors and subsequent intracellular cascades play a pivotal role in the development of opioid tolerance. Postsynaptic density protein-95 (PSD-95), a molecular scaffolding protein, assembles a specific set of signaling proteins around NMDA receptors at neuronal synapses. The current study investigated the possible involvement of PSD-95 in the development of opioid tolerance. Opioid tolerance was induced by intrathecal injection of morphine sulfate (20 μg/10 μl) twice a day for 4 consecutive days. Co-administration of morphine twice daily and PSD-95 antisense oligodeoxynucleotide (50 μg/10 μl) once daily for 4 days not only markedly reduced the PSD-95 expression and its binding to NMDA receptors in spinal cord but also significantly prevented the development of morphine tolerance. In contrast, co-administration of morphine twice daily and PSD-95 missense oligodeoxynucleotide (50 μg/10 μl) once daily for 4 days did not produce these effects. The PSD-95 antisense oligodeoxynucleotide at the doses we used did not affect baseline response to noxious thermal stimulation or locomotor function. The present study indicates that the deficiency of spinal cord PSD-95 attenuates the development of opioid tolerance. These results suggest that PSD-95 might be involved in the central mechanisms of opioid tolerance and provide a possible new target for prevention of development of opioid tolerance.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 11-15 |
| Number of pages | 5 |
| Journal | Neuroscience |
| Volume | 123 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2004 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
Keywords
- Antisense technology
- Hyperalgesia
- Intrathecal injection
- NMDA receptors
- Opioid tolerance
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Knockdown of spinal cord postsynaptic density protein-95 prevents the development of morphine tolerance in rats. / Liaw, W. J.; Zhang, B.; Tao, F.; Yaster, M.; Johns, R. A.; Tao, Y. X.
In: Neuroscience, Vol. 123, No. 1, 01.01.2004, p. 11-15.Research output: Contribution to journal › Article
TY - JOUR
T1 - Knockdown of spinal cord postsynaptic density protein-95 prevents the development of morphine tolerance in rats
AU - Liaw, W. J.
AU - Zhang, B.
AU - Tao, F.
AU - Yaster, M.
AU - Johns, R. A.
AU - Tao, Y. X.
PY - 2004/1/1
Y1 - 2004/1/1
N2 - The activation of spinal cord N-methyl-D-aspartate (NMDA) receptors and subsequent intracellular cascades play a pivotal role in the development of opioid tolerance. Postsynaptic density protein-95 (PSD-95), a molecular scaffolding protein, assembles a specific set of signaling proteins around NMDA receptors at neuronal synapses. The current study investigated the possible involvement of PSD-95 in the development of opioid tolerance. Opioid tolerance was induced by intrathecal injection of morphine sulfate (20 μg/10 μl) twice a day for 4 consecutive days. Co-administration of morphine twice daily and PSD-95 antisense oligodeoxynucleotide (50 μg/10 μl) once daily for 4 days not only markedly reduced the PSD-95 expression and its binding to NMDA receptors in spinal cord but also significantly prevented the development of morphine tolerance. In contrast, co-administration of morphine twice daily and PSD-95 missense oligodeoxynucleotide (50 μg/10 μl) once daily for 4 days did not produce these effects. The PSD-95 antisense oligodeoxynucleotide at the doses we used did not affect baseline response to noxious thermal stimulation or locomotor function. The present study indicates that the deficiency of spinal cord PSD-95 attenuates the development of opioid tolerance. These results suggest that PSD-95 might be involved in the central mechanisms of opioid tolerance and provide a possible new target for prevention of development of opioid tolerance.
AB - The activation of spinal cord N-methyl-D-aspartate (NMDA) receptors and subsequent intracellular cascades play a pivotal role in the development of opioid tolerance. Postsynaptic density protein-95 (PSD-95), a molecular scaffolding protein, assembles a specific set of signaling proteins around NMDA receptors at neuronal synapses. The current study investigated the possible involvement of PSD-95 in the development of opioid tolerance. Opioid tolerance was induced by intrathecal injection of morphine sulfate (20 μg/10 μl) twice a day for 4 consecutive days. Co-administration of morphine twice daily and PSD-95 antisense oligodeoxynucleotide (50 μg/10 μl) once daily for 4 days not only markedly reduced the PSD-95 expression and its binding to NMDA receptors in spinal cord but also significantly prevented the development of morphine tolerance. In contrast, co-administration of morphine twice daily and PSD-95 missense oligodeoxynucleotide (50 μg/10 μl) once daily for 4 days did not produce these effects. The PSD-95 antisense oligodeoxynucleotide at the doses we used did not affect baseline response to noxious thermal stimulation or locomotor function. The present study indicates that the deficiency of spinal cord PSD-95 attenuates the development of opioid tolerance. These results suggest that PSD-95 might be involved in the central mechanisms of opioid tolerance and provide a possible new target for prevention of development of opioid tolerance.
KW - Antisense technology
KW - Hyperalgesia
KW - Intrathecal injection
KW - NMDA receptors
KW - Opioid tolerance
UR - http://www.scopus.com/inward/record.url?scp=0344255683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344255683&partnerID=8YFLogxK
U2 - 10.1016/j.neuroscience.2003.09.007
DO - 10.1016/j.neuroscience.2003.09.007
M3 - Article
C2 - 14667437
AN - SCOPUS:0344255683
VL - 123
SP - 11
EP - 15
JO - Neuroscience
JF - Neuroscience
SN - 0306-4522
IS - 1
ER -