Quantitative autoradiography of adenosine receptors in brains of chronic naltrexone‐treated mice

Manipulation of μ opioid receptor expression either by chronic morphine treatment or by deletion of the gene encoding μ opioid receptors leads to changes in adenosine receptor expression. Chronic administration of the opioid receptor antagonist naltrexone leads to upregulation of μ receptor binding in the brain. To investigate if there are any compensatory alterations in adenosine systems in the brains of chronic naltrexone‐treated mice, we carried out quantitative autoradiographic mapping of A 1 and A 2A adenosine receptors in the brains of mice treated for 1 week with naltrexone (8 mg −1 kg −1 day −1 ), administered subcutaneously via osmotic minipump. Adjacent coronal brain sections were cut from chronic saline‐ and naltrexone‐treated mice for the determination of binding of [ 3 H] D ‐Ala 2 ‐MePhe 4 ‐Gly‐ol 5 enkephalin ([ 3 H] DAMGO), [ 3 H]1,3‐dipropyl‐8‐cyclopentylxanthine ([ 3 H] DPCPX) or [ 3 H] 2‐[ p ‐(2‐carbonylethyl)phenylethylamino]‐5′‐ N ‐ethylcarboxamidoadenosine ([ 3 H] CGS21680) to μ , A 1 and A 2A receptors, respectively. A significant increase in μ and A 1 receptor binding was detected in chronic naltrexone‐treated brains. The changes in μ receptors were significant in several regions, but changes in A 1 were relatively smaller but showed significant upregulation collectively. No significant change in A 2A receptor binding was detected in chronic naltrexone‐treated brains. The results show that blockade of opioid receptors causes upregulation of A 1 receptors, but not A 2A receptors, by as yet undefined mechanisms.British Journal of Pharmacology (2003) 139 , 1187–1197. doi: 10.1038/sj.bjp.0705340