Lithium inhibits the development of physical dependence to clonidine in mice.
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.
Dehpour
Ahmad Reza
AR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran. Dehpour@yahoo.com
Sadr
Seyed Shahabeddin
SS
Azizi
Mahtab Roohi
MR
Namiranian
Khodadad
K
Farahani
Mehrdad
M
Javidan
Abbas Nowroozy
AN
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
D000317:Adrenergic alpha-Antagonists; D009292:Narcotic Antagonists; D015016:Yohimbine; D009270:Naloxone; D009020:Morphine; D008094:Lithium; D003000:Clonidine