Effects of alpha 2-agonists on morphine withdrawal behaviour: potentiation of jumping mediated by alpha 2-receptors.

Abstract

Clonidine has a dual action on naloxone-precipitated morphine withdrawal symptoms in rats: a suppressive action on body shakes and body weight loss and a potentiating action on jumping and aggression. It has been suggested that this potentiating, excitatory action is mediated by alpha 1-receptors. More specific alpha 2-agonists therefore should have a less excitatory effect on the latter symptoms. This hypothesis has been studied in rats dependent on morphine. Withdrawal was precipitated using naloxone. Prior to naloxone the alpha 2-agonists clonidine, guanfacine, azepexole, BHT-920, UK 14304 or the centrally acting alpha 1-agonist ST 587 were administered. All alpha 2-agonists but not the alpha 1-agonist potentiated the jumping and decreased body shakes and body weight loss. The effects of clonidine and azepexole were characterized pharmacologically using the alpha-antagonists yohimbine and prazosin. Jumping potentiated by clonidine was antagonized by yohimbine whereas prazosin had no effect. Azepexole induced jumping was decreased by yohimbine both with respect to incidence and frequency, whereas prazosin only lowered the frequency. The suppressive actions of clonidine and azepexole on body shakes were reversed by yohimbine and not by prazosin. The data indicate that the potentiation of jumping by alpha 2-agonists as well as the suppression of body shakes in morphine withdrawal behaviour is mediated by alpha 2-receptors.