Alpha-2 agonists decrease expression of morphine-induced conditioned place preference.

Opioidergic system can interact with different transmission such as dopaminergic and adrenergic system. It has been shown that alpha-adrenergic system is involved in some effects of opioid including reward. In this study, alpha-2 agonists were used before testing on day 6 to evaluate their effects on the expression of morphine-induced conditioned place preference (CPP). Our results showed that intraperitoneal (i.p.) injections of morphine (5 mg/kg) induced CPP. Administration of alpha(2)-agonists clonidine (0.01, 0.02 and 0.04 mg/kg, i.p.), tizanidine (0.1, 0.2 and 0.4 mg/kg, i.p.) and xylazine (2.5, 5 and 10 mg/kg, i.p.) decreases the expression of morphine-induced CPP. Yohimbine (0.5 mg/kg, i.p.) reversed the inhibitory effect of alpha(2)-agonists. The comparison of potency of inhibitory effect of three agonists showed that ID(50) values for clonidine, tizanidine and xylazine were 0.013, 0.32 and 1.86 mg/kg respectively. Therefore, it is concluded that alpha(2)-agonists decrease the morphine-induced CPP in mice and clonidine is more potent than tizanidine and xylazine. The relative potency of clonidine with respect to tizanidine and xylazine was 30 and 180 respectively.