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.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018492:Dopamine Antagonists; D004357:Drug Synergism; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D019966:Substance-Related Disorders / Q000503:physiopathology
D000317:Adrenergic alpha-Antagonists; D001381:Azepines; D018492:Dopamine Antagonists; D010879:Piperazines; D009020:Morphine; C015603:azepexole; D006220:Haloperidol; D003000:Clonidine; C015068:1-(3-chlorophenyl)piperazine