Journal
DRUG AND ALCOHOL DEPENDENCE
Volume 88, Issue 1, Pages 36-41Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.drugalcdep.2006.09.010
Keywords
chemokine receptors; chemokine ligands; opioid receptors; opioid agonists; heterologous desensitization; rat
Categories
Funding
- NIDA NIH HHS [DA06650, R01 DA014230, R01 DA006650, DA11130, DA14230, DA13429, P30 DA013429, R01 DA016544, DA16544] Funding Source: Medline
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Previous studies have shown pretreatment with chemokines CCL5/RANTES (100ng) or CXCL12/SDF-1alpha (100ng) injected into the peri-aqueductal grey (PAG) region of the brain, 30 min before the mu opioid agonist DAMGO (400 ng), blocked the antinociception induced by DAMGO in the in vivo cold water tail-flick (CWT) antinociceptive test in rats. In the present experiments, we tested whether the action of other agonists at mu and delta opioid receptors is blocked when CCL5/RANTES or CXCL12/SDF-1alpha is administered into the PAG 30 min before, or co-administered with, opioid agonists in the CWT assay. The results showed that: (1) CXCL12/SDF-1alpha (100 ng, PAG) or CCL5/RANTES (100 ng, PAG), given 30 min before the opioid agonist morphine, or selective delta opioid receptor agonist DPDPE, blocked the antinociceptive effect of these drugs; (2) CXCL12/SDF-1alpha (100 ng, PAG) or CCL5/RANTES (100 ng, PAG), injected at the same time as DAMGO or DPDPE, significantly reduced the antinociceptive effect induced by these drugs. These results demonstrate that the heterologous desensitization is rapid between the mu or delta opioid receptors and either CCL5/RANTES receptor CCR5 or CXCL12/SDF-1alpha receptor CXCR4 in vivo, but the effect is greater if the chemokine is administered before the opioid. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
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