CHRONIC INTRACEREBROVENTRICULAR ADMINISTRATION OF MORPHINE DOWN-REGULATES SPINAL ADENOSINE A(1) RECEPTORS IN RATS

Previous studies from our laboratory have shown that systemic chronic morphine treatment causes down-regulation of spinal adenosine A(1) receptors in rats. In this study, we further investigated whether supraspinal morphine treatment causes this effect. Adult male Sprague-Dawley rats were rendered tolerant to morphine by multiple intracerebroventricular (i.c.v.) injections for 2 or 4 days. Adenosine A(1) receptor binding activities were measured with [H-3]cyclohexyladenosine in the spinal cord and midbrain. A significant decrease in [H-3]cyclohexyladenosine binding was found in the spinal cord but not in the midbrain region after 2 or 4 days of chronic i.c.v. morphine treatment. A decrease in the number of binding sites (B-max) with no change in the affinity (K-d) of the ligand for the adenosine A(1) receptor was observed. These results suggest that supraspinal morphine administration could cause the down-regulation of spinal adenosine A(1) receptors and this may play a role in the mechanism of morphine tolerance.