Enhanced morphine withdrawal and μ-opioid receptor G-protein coupling in A2A adenosine receptor knockout ti ice

被引:37
作者
Bailey, A
Davis, L
Lesscher, HMB
Kelly, MDW
Ledent, C
Hourani, SMO
Kitchen, I [1 ]
机构
[1] Univ Surrey, Sch Biomed & Mol Sci, Pharmacol Grp, Guildford GU2 7XH, Surrey, England
[2] Free Univ Brussels, Inst Rech Interdisciplinaire Biol Humaine & Nucl, Brussels, Belgium
关键词
S-35]GTP gamma S; mu-opioid receptor; A(2A) knockout; autoradiography; D2; receptor; withdrawal;
D O I
10.1046/j.1471-4159.2003.02214.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, g-opioid and dopamine D-2 receptor auto radiography, as well as mu-opioid receptor-stimulated guanylyl 5'-[gamma-[S-35]thio]-triphosphate ([S-35]GTPgammaS) autoradiography was carried out in brain sections of withdrawn wild-type and knockout mice. No significant changes in D-2 and mu-opioid receptor binding were observed in any of the brain regions analysed. However, a significant increase in the level of mu receptor-stimulated [S-35]GTPgammaS binding was observed in the nucleus accumbens of withdrawn knockout mice.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.
引用
收藏
页码:827 / 834
页数:8
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