The β2 adrenergic receptor regulates morphine tolerance and physical dependence
Adaptations to the chronic administration of opioids reduce the utility of these drugs in treating pain and support addiction. Recent genetics-based approaches have implicated the β2 adrenergic receptor (β2-AR) in controlling some of these responses. We do not know, however, whether this receptor ca...
Saved in:
Published in | Behavioural brain research Vol. 181; no. 1; pp. 118 - 126 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
Shannon
Elsevier B.V
19.07.2007
Elsevier Science |
Subjects | |
Online Access | Get full text |
Cover
Loading…
Summary: | Adaptations to the chronic administration of opioids reduce the utility of these drugs in treating pain and support addiction. Recent genetics-based approaches have implicated the β2 adrenergic receptor (β2-AR) in controlling some of these responses. We do not know, however, whether this receptor can modulate tolerance, dependence or changes in gene expression caused by chronic opioid administration. For our studies we used C57BL/6 mice and β2-AR knockout mice in the FVB background. Morphine dose–response relationships were established both prior to and after chronic morphine treatment. In some cases, the selective β2-AR antagonist butoxamine was administered along with or after morphine. Physical dependence was assessed using naloxone-precipitated withdrawal. The expression of calcitonin gene related peptide (CGRP) and substance P (SP) were measured in spinal cord and dorsal root ganglion (DRG) tissues using both real-time PCR and enzyme-linked immunoassay (ELISA). Both the co-administration of butoxamine with morphine and the administration of butoxamine after chronic morphine reversed morphine tolerance. Morphine failed to cause tolerance in β2-AR knockout mice. Physical dependence was reduced under the same circumstances. The chronic administration of butoxamine with morphine reduced or eliminated the normally observed up-regulation of CGRP and SP in spinal cord and DRG tissues. Our results suggest that the β2-AR modulates both opioid tolerance and physical dependence. Activation of β2-ARs appears to be required for some of the key neurochemical changes which characterize chronic opioid administration. Therefore, β2-AR antagonists show some promise as agents to enhance chronic opioid analgesic therapy. |
---|---|
ISSN: | 0166-4328 1872-7549 |
DOI: | 10.1016/j.bbr.2007.03.037 |