Dipropylacetate-induced quasi-morphine abstinence behaviour in the rat: suppression by alpha 2-adrenoceptor stimulation.
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.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000503:physiopathology*; D014635:Valproic Acid / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D014635:Valproic Acid; D009020:Morphine; D003000:Clonidine