The potentiation of morphine-withdrawal jumping by clonidine is antagonized by m-chlorophenylpiperazine and not by haloperidol.

Administration of naloxone (0.5 mg/kg i.p.) to morphine-dependent rats induced a strong withdrawal syndrome consisting of body shakes, escape jumping and various autonomic signs. Clonidine (750 micrograms/kg s.c.) had a dual action on naloxone-precipitated withdrawal symptoms in rats: a suppressive action on body shakes and a potentiating action on jumping. Both actions were found to be mediated by alpha 2-receptors which generally are responsible for sedative effects. Therefore, the action of alpha 2-agonists such as clonidine and azepexole was studied more extensively. Since both serotonergic and dopaminergic systems have been suggested to be involved in morphine-withdrawal jumping, the interaction of clonidine and azepexole with serotonergic and dopaminergic drugs was studied. Neither haloperidol (0.3 mg/kg i.p.) nor the benzamides sulpiride (40 mg/kg p.o.) and metoclopramide (8 mg/kg i.p.) affected the jumping potentiated by the alpha 2-agonists. However, the serotonin-agonist m-chlorophenylpiperazine (2.5 mg/kg i.p.) suppressed the effects of clonidine. Precipitation of jumping in morphine-dependent animals was more effective using bremazocine (1.0 mg/kg i.p.). This effect again could be potentiated by clonidine (750 micrograms/kg s.c.). A low dose of m-chlorophenylpiperazine (0.03 mg/kg i.p.) antagonized the clonidine-effect without affecting the basal jumping response. The data suggest that clonidine potentiates naloxone-precipitated jumping by decreasing serotonergic output while the administration of m-chlorophenylpiperazine can counteract this lack of serotonergic activity.