Mice lacking rhes show altered morphine analgesia, tolerance, and dependence

Rhes, the Ras Homolog Enriched in Striatum, is an intermediate-size GTP binding protein. Although its full functions are not yet known, it has been shown to affect signaling and behaviors mediated by G protein-coupled receptors. Here we have tested whether Rhes affects behaviors mediated by opioid receptors. Wild type and rhes-deficient mice were administered morphine and tested for analgesia in formalin and tail flick tests. Rhes(-/-) mice showed significantly enhanced analgesia in both tests relative to rhes(+/+) mice. Furthermore, rhes(-/-) mice did not display tolerance to repeated morphine administration and displayed significantly less withdrawal than rhes(+/+) mice. These findings indicate that Rhes is involved in behaviors mediated by mu opioid receptors and in the adaptive response to repeated morphine administration. (C) 2010 Elsevier Ireland Ltd. All rights reserved.