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

1 Manipulation of m opioid receptor expression either by chronic morphine treatment or by deletion of the gene encoding m opioid receptors leads to changes in adenosine receptor expression. Chronic administration of the opioid receptor antagonist naltrexone leads to upregulation of m receptor binding in the brain. 2 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. 3 Adjacent coronal brain sections were cut from chronic saline- and naltrexone-treated mice for the determination of binding of [H-3] d-Ala(2)-MePhe(4)-Gly-ol(5) enkephalin ([H-3] DAMGO), [H-3] 1,3-dipropyl- 8-cyclopentylxanthine ([H-3] DPCPX) or [H-3]2-[p-(2-carbonylethyl) phenylethylamino]-5'-N-ethylcarboxamidoadenosine ([H-3] CGS21680) to mu, A(1) and A(2A) receptors, respectively. 4 A significant increase in mu and A(1) receptor binding was detected in chronic naltrexone-treated brains. The changes in m 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. 5 The results show that blockade of opioid receptors causes upregulation of A(1) receptors, but not A(2A) receptors, by as yet undefined mechanisms.