title: Mice lacking rhes show altered morphine analgesia, tolerance, and dependence.
abstract: 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.
authors.affiliation: Department of Psychology, University of New Orleans, New Orleans, LA 70148, USA.
authors.forename: Franklin A
authors.initials: FA
authors.lastname: Lee
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Baiamonte
authors.forename: Daniela
authors.initials: D
authors.lastname: Spano
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Lahoste
authors.forename: R Denis
authors.initials: RD
authors.lastname: Soignier
authors.forename: Laura M
authors.initials: LM
authors.lastname: Harrison
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009021:Morphine Dependence / Q000235:genetics*; D010146:Pain / Q000188:drug therapy / Q000235:genetics*; D010147:Pain Measurement / Q000379:methods; D013375:Substance Withdrawal Syndrome / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine; D019204:GTP-Binding Proteins; C488189:Rasd2 protein, mouse