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Knockdown of spinal cord postsynaptic density protein-95 prevents the development of morphine tolerance in rats
- Source :
-
Neuroscience . Jan2004, Vol. 123 Issue 1, p11. 5p. - Publication Year :
- 2004
-
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. [Copyright &y& Elsevier]
- Subjects :
- *SPINAL cord
*METHYL aspartate
*OPIOIDS
*PROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 03064522
- Volume :
- 123
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 11656735
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2003.09.007