Purinoreceptors are involved in the control of acute morphine withdrawal

The effects exerted by P1 and P2 purinoceptor agonists and antagonists on t he acute opiate withdrawal induced by morphine were investigated in vitro. Following a 4 min in vitro exposure to morphine, the guinea-pig isolated il eum exhibited a strong contracture after the addition of naloxone. The P1 p urinoceptor agonist, adenosine, was able dose-dependently to reduce morphin e withdrawal whereas alpha,beta -methylene ATP (APCPP), a P2 purinoceptor a gonist, increased morphine withdrawal. Caffeine, a Pl purinoceptor antagoni st, was able significantly and in a concentration dependent manner to incre ase morphine withdrawal whereas quinidine, a P2 receptor antagonist, reduce d it. The results of our experiments indicate that both P1 and P2 purinocep tor agonists and antagonists are able to influence opiate withdrawal in vit ro, suggesting an important functional interaction between the purinergic s ystem and opioid withdrawal. (C) 2001 Elsevier Science Inc. All rights rese rved.