EFFECT OF ORAL YOHIMBINE ON WITHDRAWAL JUMPING BEHAVIOR OF MORPHINE-DEPENDENT MICE

Acute administration of the alpha-2 adrenoceptor agonist clonidine and chronic administration of the alpha-2 antagonist yohimbine both inhib it opioid withdrawal signs in experimental models of dependence and al so in clinical studies with opiate abusers. There are exceptions to th is general rule: restlessness or self-reported abstinence in humans an d withdrawal-induced escape behaviour in rodents are resistant to inhi bition by acute clonidine. We have explored the effect of the alpha-2 antagonist yohimbine on morphine withdrawal-induced escape behaviour i n a mouse model that we have proposed to differentiate between the urg e to escape (number of jumps) and non-specific sedative/motor actions (height of jumps). Morphine dependence was induced by s.c. administrat ion of a sustained-release preparation (I g/kg). Naloxone (1 mg/kg) wa s injected to precipitate withdrawal jumping 72 hours after morphine i njection. Go-treatment with yohimbine dissolved in the tap water (70 m g/l) decreased the number of jumps upon naloxone challenge, an effect which did not seem to be related with a sedative or toxic effect of th e drug. This result confirms previous data and suggests that yohimbine could prevent the development of opioid dependence being active to de crease withdrawal-induced escape behaviour. The mechanisms of this act ion are discussed.