Enhanced morphine withdrawal and micro -opioid receptor G-protein coupling in A2A adenosine receptor knockout mice.
Much evidence supports the hypothesis that A2A adenosine receptors play an important role in the expression of morphine withdrawal and that the dopaminergic system might also be involved. We have evaluated morphine withdrawal signs in wild-type and A2A receptor knockout mice and shown a significant enhancement in some withdrawal signs in the knockout mice. In addition, micro -opioid and dopamine D2 receptor autoradiography, as well as micro -opioid receptor-stimulated guanylyl 5'-[gamma-[35S]thio]-triphosphate ([35S]GTPgammaS) autoradiography was carried out in brain sections of withdrawn wild-type and knockout mice. No significant changes in D2 and micro -opioid receptor binding were observed in any of the brain regions analysed. However, a significant increase in the level of micro receptor-stimulated [35S]GTPgammaS binding was observed in the nucleus accumbens of withdrawn knockout mice. These data indicate that the A2A receptor plays a role in opioid withdrawal related to functional receptor activation.
Bailey
Alexis
A
Pharmacology group, School of Biomedial and Molecular Sciences, University of Surrey, Guildford, Surrey, UK.
Davis
Lianne
L
Lesscher
Heidi M B
HM
Kelly
Mary D W
MD
Ledent
Catherine
C
Hourani
Susanna M O
SM
Kitchen
Ian
I
D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D003720:Densitometry / Q000379:methods; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000493:pharmacokinetics; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000627:therapeutic use; D009292:Narcotic Antagonists; D020891:Raclopride / Q000493:pharmacokinetics; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D013460:Sulfur Isotopes / Q000493:pharmacokinetics; D014202:Tremor / Q000139:chemically induced / Q000188:drug therapy; D014316:Tritium / Q000493:pharmacokinetics; D014556:Urine / Q000502:physiology; D015431:Weight Loss / Q000187:drug effects
D009292:Narcotic Antagonists; D043705:Receptor, Adenosine A2A; D017450:Receptors, Opioid, mu; D013460:Sulfur Isotopes; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020891:Raclopride; D009020:Morphine; D019204:GTP-Binding Proteins