title: Lithium inhibits the development of physical dependence to clonidine in mice.
abstract: Based on our previous finding that chronic lithium treatment reduced naloxone-precipitated withdrawal syndrome in morphine-treated mice, the effect of chronic lithium treatment was evaluated on the development of dependence to clonidine. Dependence was induced by injection of either morphine (50, 50 and 75 mg/kg, intraperitoneally with 3 hr interval for 3 consecutive days), or clonidine (2 mg/kg/day, intraperitoneally for 10 days). Naloxone (4 mg/kg, intraperitoneally) precipitated withdrawal signs in both morphine- and clonidine-treated mice. Yohimbine (5 mg/kg, intraperitoneally) precipitated withdrawal signs in the clonidine-treated mice, similar to morphine withdrawal signs; but failed to precipitate any significant sign in the morphine-treated mice. Coadministration of lithium was carried out by adding lithium chloride to drinking water (600 mg/l for 20 days; 10 days before the beginning of clonidine administration and 17 days before the administration of morphine to allow the lithium concentration to reach steady-state). The results indicated that chronic lithium administration significantly attenuated the withdrawal signs, precipitated either by yohimbine or naloxone, in clonidine-treated mice. As a conclusion, clonidine withdrawal signs are very similar to opioid withdrawal signs, and lithium is able to prevent the development of physical dependence to clonidine.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran. Dehpour@yahoo.com
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
authors.forename: Seyed Shahabeddin
authors.initials: SS
authors.lastname: Sadr
authors.forename: Mahtab Roohi
authors.initials: MR
authors.lastname: Azizi
authors.forename: Khodadad
authors.initials: K
authors.lastname: Namiranian
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Farahani
authors.forename: Abbas Nowroozy
authors.initials: AN
authors.lastname: Javidan
mesh_terms: D000284:Administration, Oral; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009020:Morphine / Q000633:toxicity; D009021:Morphine Dependence / Q000209:etiology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D019966:Substance-Related Disorders / Q000209:etiology*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D009292:Narcotic Antagonists; D015016:Yohimbine; D009270:Naloxone; D009020:Morphine; D008094:Lithium; D003000:Clonidine