Chronic intrathecal morphine treatment does not cause down-regulation of spinal adenosine A1 receptors in rats.

Abstract

We have shown previously that systemic chronic morphine treatment causes down-regulation of spinal adenosine A1 receptors in rats. Recently, we have found that chronic supraspinal morphine treatment also causes this effect. In the present study, we investigated whether chronic spinal morphine treatment has the same effect of down-regulation of spinal adenosine A1 receptors. Adult male Sprague-Dawley rats were rendered tolerant to morphine either by multiple intrathecal (i.t.) injections or continuous i.t. infusion by osmotic pump administration for 2 or 4 days. Spinal A1-adenosine receptor binding activity was measured by using the selective A1 adenosine agonist [3H]cyclohexyladenosine. No significant decrease in [3H]cyclohexyladenosine binding was found in the spinal cord after 2 or 4 days of multiple i.t. injections of morphine. There was also no significant change in the amount of spinal [3H]cyclohexyladenosine bound after 4 days of continuous i.t. infusion of morphine by osmotic pump. From these and our previous results, it is concluded that only supraspinal chronic morphine treatment down regulates the spinal A1 adenosine receptor and this may play a role in the mechanism of supraspinal morphine tolerance but not spinal morphine tolerance.