Evaluation of the effect of intra cerebroventricular administration of CCPA on reduction of tolerance to the analgesic effect of morphine in rat

Continuous or long term use of opiate drugs may cause tolerance to the analgesic effect of these drugs, which limits the therapeutic efficacy of these drugs. In this study we evaluated the effects of central administration of 2-chloro-N6-cyclopentyladenosine (CCPA), a selective A1 receptor agonist, on morphine-induced tolerance in rats. Different groups of rats received daily intracerebroventricular (ICV) morphine (10 mg/kg, ip) in combination with saline 5 μl/rat, or intracerebroventricular (icv) CCPA (20, 40, 80 μg/5 μl/rat). Nociception was assessed by use of a hotplate apparatus (55±0.5°C). Using a hot-plate device, the pain inducing effect was recorded when the rat licked its hind paw or jumped. Results showed that different doses of CCPA (20, 40, 80 μg/5 μl/rat, icv) delayed the tolerance to the analgesic effect of morphine for 4, 8, and 10 days respectively. In addition, our results showed that CCPA increased the total analgesic effect of morphine. We found that intracerebroventricular administration of CCPA, A1 selective agonists, prevented morphine-induced tolerance to the analgesic effect in rat.