Yohimbine exacerbates and clonidine attenuates acute morphine withdrawal in rats

The involvement of alpha 2-noradrenergic receptors in the expression of opiate withdrawal was studied using an operant behavioral model of acute morphine dependence. Clonidine, an alpha 2-agonist, attenuated and yohimbine, an alpha 2-antagonist, exacerbated the naloxone-induced suppression of fixed ratio 15 responding in rats pretreated several hours earlier with a single, moderate dose of morphine. These data indicate that the alpha 2-agonist action of clonidine is responsible for its amelioration of withdrawal symptoms. It also validates the acute dependence model for studying the pharmacology of opiates and associated adaptive processes.