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Enhanced morphine withdrawal and µ‐opioid receptor G‐protein coupling in A 2A adenosine receptor knockout mice
Author(s) -
Bailey Alexis,
Davis Lianne,
Lesscher Heidi M. B.,
Kelly Mary D. W.,
Ledent Catherine,
Hourani Susanna M. O.,
Kitchen Ian
Publication year - 2004
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02214.x
Subject(s) - knockout mouse , nucleus accumbens , receptor , dopaminergic , medicine , chemistry , opioid , morphine , endocrinology , opioid receptor , dopamine receptor , dopamine , pharmacology , biology
Much evidence supports the hypothesis that A 2A 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 A 2A receptor knockout mice and shown a significant enhancement in some withdrawal signs in the knockout mice. In addition, µ‐opioid and dopamine D 2 receptor autoradiography, as well as µ‐opioid receptor‐stimulated guanylyl 5′‐[γ‐[ 35 S]thio]‐triphosphate ([ 35 S]GTPγS) autoradiography was carried out in brain sections of withdrawn wild‐type and knockout mice. No significant changes in D 2 and µ‐opioid receptor binding were observed in any of the brain regions analysed. However, a significant increase in the level of µ receptor‐stimulated [ 35 S]GTPγS binding was observed in the nucleus accumbens of withdrawn knockout mice. These data indicate that the A 2A receptor plays a role in opioid withdrawal related to functional receptor activation.