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

• Published in: British journal of pharmacology 2003-07, Vol.139 (6), p.1187-1195
• Main Authors: Bailey, Alexis, Hawkins, Rachel M, Hourani, Susanna M O, Kitchen, Ian
• Format: Article
• Language: English
• Subjects: A1 receptor; A2A receptor; Animals; Autoradiography; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Chronic naltrexone treatment; Drug Administration Schedule; Medical sciences; Mice; Mice, Inbred C57BL; Naltrexone - administration & dosage; Naltrexone - metabolism; Protein Binding - drug effects; Protein Binding - physiology; Receptors, Opioid, mu - analysis; Receptors, Opioid, mu - metabolism; Receptors, Purinergic P1 - analysis; Receptors, Purinergic P1 - metabolism; μ opioid receptor
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1038/sj.bjp.0705340

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 A1 and A2A 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 [3H] D‐Ala2‐MePhe4‐Gly‐ol5 enkephalin ([3H] DAMGO), [3H]1,3‐dipropyl‐8‐cyclopentylxanthine ([3H] DPCPX) or [3H] 2‐[p‐(2‐carbonylethyl)phenylethylamino]‐5′‐N‐ethylcarboxamidoadenosine ([3H] CGS21680) to μ, A1 and A2A receptors, respectively. A significant increase in μ and A1 receptor binding was detected in chronic naltrexone‐treated brains. The changes in μ receptors were significant in several regions, but changes in A1 were relatively smaller but showed significant upregulation collectively. No significant change in A2A receptor binding was detected in chronic naltrexone‐treated brains. The results show that blockade of opioid receptors causes upregulation of A1 receptors, but not A2A receptors, by as yet undefined mechanisms. British Journal of Pharmacology (2003) 139, 1187–1197. doi:10.1038/sj.bjp.0705340