Effect of adenosine analogues on the expression of opiate withdrawal in rats

Abstract

The aim of this study was to test whether convergent dependence occurs in vivo. The adenosine A 1 receptor agonist N 6-[( R)]-1-methyl-2-phenylethyl]adenosine, (R-PIA), the A 2 agonist 2-(phenylamino)adenosine (CV-1808), the nonselective A 1, A 2 agonist (adenosine-5′-ethylcarboxamide (NECA), and the α 2-adrenoceptor agonist clonidine were screened (each at 30, 100, and 300 μg/kg, SC) for their ability to alter naloxine-precipitated withdrawal signs in morphine-dependent rats. The results indicate that there is convergent dependence involving opioid and adenosine A 1 receptors on those effects expressed by withdrawal diarrhoea, paw-shakes, teeth-chattering, body-shakes, and jumping. Further, dependence expressed by body-shakes involves convergence involving A 1 receptors, as well as α 2-adrenoceptors; while A 1 receptors are involved in dependence expressed by jumping, stimulation of α 2-adrenoceptors augments this signs. Adenosine analogues may be of clinical value for detoxification of opiate addicts.