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

The aim of this study was to test whether convergent dependence occurs in vivo. The adenosine A1 receptor agonist N6-[(R)-1-methyl-2-phenylethyl]adenosine (R-PIA), the A2 agonist 2-(phenylamino)adenosine (CV-1808), the nonselective A1, A2 agonist (adenosine-5'-ethylcarboxamide (NECA), and the alpha 2-adrenoceptor agonist clonidine were screened (each at 30, 100, and 300 micrograms/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 A1 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 A1 receptors, as well as alpha 2-adrenoceptors; while A1 receptors are involved in dependence expressed by jumping, stimulation of alpha 2-adrenoceptors augments this sign. Adenosine analogues may be of clinical value for detoxification of opiate addicts.