Effects of two alpha 2 agonists, rilmenidine and clonidine, on the morphine withdrawal syndrome and their potential addictive properties in rats.

The interaction between adrenergic systems and opiate receptors or neuronal systems linked to these receptors has been previously demonstrated. For this reason, clonidine can be used to reduce withdrawal syndrome to opiates. Rilmenidine (S 3341) is a new agonist of alpha 2 adrenoceptors. The purpose of these experiments was to compare the effects of rilmenidine and clonidine on morphine withdrawal syndrome and their potential addictive properties in the rat. Rats were made morphine-dependent by repeated intraperitoneal (i.p.) administration of increasing doses of morphine. Withdrawal was precipitated by injecting naloxone subcutaneously. Withdrawal scores were evaluated for 10 minutes. Clonidine (0.05, 0.1 and 0.2 mg/kg, i.p.) and rilmenidine (5 and 10 mg/kg, i.p.) significantly reduced overall withdrawal scores. Addictive potential was evaluated in the rat by a place preference test after the following treatments (mg/kg, i.p.): rilmenidine 0.1 to 5, clonidine 0.01 to 0.5, heroin 0.12, and d-amphetamine 1.5. Rilmenidine did not modify the time spent in the conditioned side at doses of 0.1 to 1 and 5 mg/kg, but increased it at 2.5 mg/kg (+25%). In contrast, a reinforcing effect was induced by clonidine (+21%, +43%, +34% at 0.1, 0.25, 0.5 mg/kg), heroin (+39%) and amphetamine (+52%). In conclusion, rilmenidine as well as clonidine reduced the morphine withdrawal syndrome. However, rilmenidine was 100 times less active than clonidine. Clonidine, heroin and d-amphetamine have clear reinforcing properties. Rilmenidine did not exhibit dose-dependent reinforcing properties and the isolated effect noted after 2.5 mg/kg is difficult to interpret because it is minor and is not observed with a higher dose.(ABSTRACT TRUNCATED AT 250 WORDS)