Evaluation the effect of intracerebroventricular injection of CPA (N6- cyclopentyladenosine) on withdrawal syndrome of morphine in rats

There are different and sometimes paradoxical reports about the effects of adenosine agonists and antagonists (specially in i.p. administration) in withdrawal syndrome of morphine. In the present study, the effects of N6-cyclopentyladenosine (CPA, A1 receptor agonist) in morphine withdrawal syndrome were investigated on NMRI rats (200- 240 g). Dependency was induced by i.p. injection of increasing doses of morphine for nine days. One hour after the last dose of morphine, withdrawal syndrome (jumping, standing on feet, abdomen writhing,wet-dog shake, genital grooming and teeth chattering) was induced by i.p. administration of naloxone. To investigate the effects of A1 receptor agonist in morphine withdrawal syndrome, CPA (20, 40, 80, μg/5μl/rat) was administered by i.c.v. route. Data were analyzed with one way anova and independent t test. CPA decreased naloxone-induced jumping-standing on feet and abdomen writhing (P<0.001) in all doses, however wetdog shake (P<0.05), teeth chattering (P<0.001) and genital grooming (P<0.01) were decreased by CPA in 40 and 80 μg/rat. The results indicate that CPA can decrease all naloxone-induced withdrawal symptoms and the effects on jumping-standing on feet, teeth chattering and genital grooming were dose-dependent.