Dipropylacetate-induced quasi-morphine abstinence behaviour in the rat: suppression by alpha 2-adrenoceptor...

The anti-withdrawal effect of clonidine was studied using quasi-morphine abstinence behaviour induced by dipropylacetate (DPA) in naive rats. Clonidine potently suppressed body shakes and locomotor activity (ID50 30 and 40 micrograms/kg IP respectively). Phenoxybenzamine and prazosine did not antagonize the anti-withdrawal effect of clonidine, whereas piperoxane and yohimbine were effective with respect to locomotor activity and a total abstinence score. Piperoxane also reversed the suppressive action of clonidine on body shakes. Other alpha 2-agonists (guanfacine, azepexole and BHT 920) also suppressed DPA-induced behaviour, whereas the lipophilic alpha 1-agonist ST-587 had such an effect only at high doses. The relative potencies of the alpha 2-agonists correlated well with their potency to exert other alpha 2-adrenoceptor mediated actions such as blood pressure lowering and sedation.