title: A comparison of the effects of digoxin, ouabain and milrinone on naloxone-precipitated withdrawal syndrome in mice.
abstract: Modulation of Na(+), K(+)-ATPase activity by acute and chronic opiates has been established for many years. However, the effects of digoxin, a putative inhibitor of Na(+), K(+)-ATPase, on naloxone-precipitated morphine withdrawal syndrome are unknown. In the present study, a digoxin dose-response curve was conducted to observe the effects on naloxone-precipitated withdrawal and locomotor activity in mice. Higher doses of digoxin (1.0 and 2.5 mg/kg) inhibited locomotor activity and naloxone-precipitated withdrawal jumping and weight loss, while lower doses of digoxin (0.1 and 0.25 mg/kg) inhibited withdrawal weight loss precipitated by naloxone without affecting locomotor activity and naloxone-precipitated withdrawal jumping. To explore the possible mechanisms underlying this behavior, another Na(+), K(+)-ATPase inhibitor ouabain, which does not cross the blood brain barrier, and another cardiotonic drug milrinone, a non-inhibitor of Na(+), K(+)-ATPase, were also included in the present study. Both milrinone and ouabain inhibited, in a dose-dependent manner, naloxone-precipitated weight loss while neither affected naloxone-precipitated withdrawal jumping nor locomotor activity in mice. These results indicate that both the cardiotonic effects and central inhibition of Na(+), K(+)-ATPase contribute to the inhibitory effects of digoxin on morphine withdrawal syndrome in mice.
authors.affiliation: Department of Clinical Pharmacology, School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Avenue, Kexue Avenue, Zhengzhou, Henan Province, China.
authors.forename: Yin-Liang
authors.initials: YL
authors.lastname: Bai
authors.forename: Qin-Jun
authors.initials: QJ
authors.lastname: Chu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Yong-Yan
authors.initials: YY
authors.lastname: Chen
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004077:Digoxin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008297:Male; D051379:Mice; D020105:Milrinone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D010042:Ouabain / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D015431:Weight Loss / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D009270:Naloxone; D010042:Ouabain; D004077:Digoxin; D009020:Morphine; D000254:Sodium-Potassium-Exchanging ATPase; D020105:Milrinone